VENCLEXTA® (venetoclax tablets) | CLL Thought Leader Videos

Hear thought leaders discuss why they choose VENCLEXTA^® (venetoclax tablets), the broad range of patient types who may receive VENCLEXTA, how to initiate VENCLEXTA, and the benefits of time off treatment.

Previously untreated CLL

Dr. Nakhle Saba talks about efficacy and safety with VENCLEXTA + GAZYVA^® (obinutuzumab) in patients with previously untreated CLL.

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VENCLEXTA CLL Portraits: A look at CLL patients and the doctors who treat them

Featuring Dr. Nakhle Saba Associate Professor of Medicine in Hematology-Oncology at Tulane University

Hypothetical patient profile. All patients and their results are different.

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PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION.

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Disclaimers:

This video is sponsored by AbbVie and Genentech, Inc., a member of the Roche Group
The healthcare provider included in this video is presenting information on behalf of AbbVie and Genentech, Inc., a member of the Roche Group

TEXT ON SCREEN:
Dr. Nakhle Saba Associate Professor of Medicine in Hematology-Oncology at Tulane University

Dr. Saba:
Hi, I’m Doctor Nakhle Saba, Associate Professor of Medicine in Hematology-Oncology at Tulane University. Today, I’d like to share a hypothetical CLL patient profile and discuss some of the factors that help me choose a treatment for my own patients.

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Cheryl, 65 years old
Patient with previously untreated chronic lymphocytic leukemia (CLL)

Hypothetical patient profile. All patients and their results are different.
Actor Portrayal

Dr. Saba:
I have seen several patients like Cheryl with previously untreated CLL.

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Comorbidities: Hypothyroidism; GERD
ECOG PS: 0
CIRS: 7
Prognostic Risk Factors: Unmutated IgVH, no 17p deletion
Other considerations: would like a treatment that best fits her lifestyle

GERD=gastroesophageal reflux disease; ECOG=Eastern Cooperative Oncology Group; PS=performance status; CIRS=cumulative illness rating scale; IGHV=immunoglobulin heavy-chain variable gene.

Dr. Saba:
Cheryl is 65 years old and her comorbidities include hypothyroidism as well as GERD. You can see the rest of her clinical background here. Considering this profile, I know I have different treatment options to choose for a patient like Cheryl. That’s why I consider the clinical profile as well as other factors, like her preference for a treatment that will best fit her lifestyle. This is something that my patients bring up to me often.

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Over 3 out of 4 respondents preferred finite-duration therapy

CLL Society Patient Preference Survey (2021)^1,2
The survey was not designed to measure preference for venetoclax fixed-duration regimens.

When 608 patients and 22 caregivers were asked about preference for duration of CLL therapy, if effectiveness and side effects were assumed similar:

77% preferred finite-duration therapy
7% preferred continuous therapy*
uMRD=undetectable minimal residual disease.
*Until disease progression or intolerance.

Survey question results:

77% preferred finite-duration therapy, which includes:
- 63% who responded "Limited duration therapy that is stopped after reaching uMRD or preplanned period of time if uMRD is not reached"
- 14% who responded "Limited duration therapy that is stopped after a preplanned period of time"
10% No preference for the duration of therapy
7% Therapy that is taken indefinitely
6% Don't know/not sure

Limitations include the opt-in sample where the survey results may not be reflective of the general CLL population and their caregivers.

Dr. Saba:
In Cheryl’s case, her profile reminds me of a recent survey from the CLL Society. Although the survey is not related to any particular therapy, it showed that a majority of patients preferred a finite-duration therapy. I think it’s important to take patient preferences into account.

Dr. Saba:
Looking at all aspects of Cheryl’s profile, I would strongly consider VENCLEXTA plus GAZYVA due to this regimen’s proven efficacy and safety. This regimen offers a chance for durable progression-free survival without continuous treatment, which can mean a patient like Cheryl has a chance to get back to a life without a daily reminder of her treatment and disease.

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VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Continue viewing for Important Safety Information at the end of the video.

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Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment.

Dr. Saba:

VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Continue viewing for Important Safety Information at the end of the video.

Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment.
Warnings and precautions include tumor lysis syndrome, neutropenia, infections, immunizations, embryo-fetal toxicity, and increased mortality in patients with multiple myeloma when VENCLEXTA is added to bortezomib and dexamethasone.
Appropriate precautions should be taken by the healthcare provider.

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Dr. Nakhle Saba Associate Professor of Medicine in Hematology-Oncology at Tulane University Medical

Dr. Saba:
VENCLEXTA regimens offer my patients proven efficacy and a well-studied safety profile.
VENCLEXTA regimens also offer patients the chance for time off treatment and no ongoing treatment exposure.

And because VENCLEXTA is a fixed-duration treatment, it can mean my patients won’t have ongoing VENCLEXTA regimen out-of-pocket costs.

The VENCLEXTA regimen offers the chance for durable progression-free survival, or PFS, without continuous treatment for someone like Cheryl, and many of my patients like to have this as an option.

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CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS OOP=out of pocket.

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[VEN+G IN PREVIOUSLY UNTREATED CLL GRAPHIC]

Treatment duration and treatment-free period are not to scale and may vary by patient.

Not representative of all patients. Patients may require multiple lines of treatment.

No comparative safety or efficacy conclusions regarding VENCLEXTA regimens and TTP regimens can be drawn from the visual. Presentation of this information is not to imply that VENCLEXTA regimens and TTP regimens are interchangeable or therapeutically equivalent.

TTP=treat to progression; VEN+G=VENCLEXTA + GAZYVA.

VEN+G regimen: Designed to be completed after 12 months (twelve 28-day treatment cycles). GAZYVA is administered in Cycles 1-6, and VENCLEXTA is taken orally 400 mg/day from Cycle 3, Day 1, after the first two cycles of GAZYVA and the 5-week VENCLEXTA dose ramp-up.³

Dr. Saba:
With a VENCLEXTA plus GAZYVA, or VEN+G regimen, Cheryl would have 1 year of treatment and then a chance for a treatment-free period. That durable PFS without long-term treatment can give her the chance to return to life without a daily reminder of her treatment and disease. With treat-to-progression options, patients receive continuous treatment until progression or unacceptable toxicity, which may result in indefinite treatment. While I use these options as well, patients like Cheryl often prefer a limited-duration treatment.

The VENCLEXTA regimen offers durable PFS with over 6 years of follow-up data in the CLL14 study. Some patients achieved PFS with 5 years off treatment. I’ve seen similar efficacy and safety results.

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CLL14 trial design: a randomized clinical trial of 432 patients (VEN+G: N=216; GClb: N=216) with previously untreated CLL.³

IRC-assessed PFS (primary endpoint)³

67% reduction in risk of progression or death vs GClb (HR=0.33; 95% Cl: 0.22-0.51 [P<0.0001])

After a median follow-up of 28 months (range: 0-36 months):

There were 29 events in the VEN+G arm (14 progressions and 15 deaths without disease progression) compared with 79 events in the GClb arm (71 progressions and 8 deaths without disease progression)^*
Median PFS was not reached in either arm

^*Number of events based on earliest event of disease progression or deaths without disease progression due to any cause.

GClb=GAZYVA + chlorambucil; IRC=independent review committee; HR=hazard ratio; Cl=confidence interval.

Dr. Saba:
CLL14 was a multicenter, randomized, open-label, phase 3 trial that evaluated progression-free survival at the primary endpoint of VEN+G versus GAZYVA plus chlorambucil, or G chlorambucil, in previously untreated CLL. In CLL14, VEN+G demonstrated durable PFS without long-term treatment. VEN+G reduced the risk of disease progression or death without disease progression by 67% versus G chlorambucil. Median progression-free survival was not reached in either arm.

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[6-YEAR FOLLOW-UP ANALYSIS OF INV-ASSESSED PFS TABLE]

6-year follow-up analysis of INV-assessed PFS (overall follow-up of 86.5 months)⁴*

PFS estimates may be unreliable at the tail end of the curve due to smaller number of patients at risk

*Based on data as of clinical data cutoff date of November 14, 2022; time of analysis was not pre-specified.
INV=investigator; TTNT=time to next treatment.
The PFS and TTNT follow-up analyses were not tested for statistical significance⁴

With a median follow-up of 76.4 months (range: 0-86.5 months), median PFS was estimated to be 76.2 months (95% Cl. 65.1-83.3) for the VEN+G arm and 36.4 months (95% Cl: 34.1-41.0) in the GClb arm (HR=0.40; 95% Cl: 0.31-0.52)
Of the 101 events In the VEN+G arm, 67 were disease progression, and 34 were deaths without disease progression. Of the 161 events In the GClb arm, 141 were disease progression, and 20 were deaths without disease progression

Dr. Saba:
The estimated 6-year progression-free survival rate was 53% for VEN+G, versus 22% for G chlorambucil. This means some patients were progression-free for 5 years after just 1 year of treatment.

And in a 6-year follow-up analysis of time to next treatment, at the time of the analysis, 64% of patients in the VEN+G arm had not received subsequent treatment (versus 35% of patients in the G chlorambucil arm). That means 6 out of 10 patients still did not require the next line of therapy 5 years after completing first-line treatment with VEN+G, which may be important to consider for a patient like Cheryl who is concerned about ongoing therapy.

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The National Comprehensive Cancer Network^® (NCCN^®) recommends certain venetoclax (VENCLEXTA^®) combination regimens as Category 1 preferred treatment options for CLL/SLL*⁵

For first-line CLL/SLL, in patients without del(17p)/TP53 mutation Venetoclax + obinutuzumab (GAZYVA^®) Category 1 preferred
For second-line and subsequent therapy Venetoclax + rituximab Category 1 preferred

NCCN is a trademark owned by the National Comprehensive Cancer Network^® (NCCN^®).
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
*See NCCN Guidelines^® for the NCCN definitions of Categories of Preference and Categories of Evidence and Consensus.

Dr. Saba:
I’m also encouraged that the National Comprehensive Cancer Network recommends these VENCLEXTA regimens as a Category 1 preferred treatment option for patients with CLL.

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[ADVERSE REACTIONS BY BODY SYSTEM TABLE]

*Includes multiple adverse reaction terms.
VEN+G=VENCLEXTA+GAZYVA; GClb=GAZYVA+chlorambucil.

Dr. Saba:
I always discuss with my patients the risks associated with the VENCLEXTA regimen. The most common adverse reactions in the CLL14 trial were neutropenia, diarrhea, and fatigue.

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[GRADE 3/4 AEs GRAPHIC] (%)^4*†
GRADE 3/4 AEs (%)^4*†

Other important Grade 3/4 AEs
- Febrile neutropenia: 4% during combination-therapy period, 0% during single-agent period, 1% during off treatment period
- Pneumonia: 3% during combination-therapy period, 1% during single-agent period, 3% during off-treatment period
- TLS: 1% during combination-therapy period, 0% during single-agent period, 0% during off treatment period
VEN+G combination-therapy period (6 cycles): Includes Grade 3 and 4 treatment-emergent AEs occurring on or before last exposure date of GAZYVA + 29 days
VENCLEXTA single-agent period (6 cycles): Includes Grade 3 and 4 AEs occurring after the start of the VEN monotherapy period to last date of VEN + 29 days
Off treatment: Includes Grade 3 and 4 AEs occurring after 29 days and up to 6 months after treatment completion
Multiple occurrences of the same AE in an individual during the same treatment period are counted only once for that treatment period

*Based on data as of clinical cutoff date of November 14, 2022.
^†The chart reflects Grade 3/4 AEs with incidence ≥5%.
AE=adverse event; TLS=tumor lysis syndrome.

Dr. Saba:
Here you see the incidence of Grade 3 and 4 adverse events from the 6-year follow-up of the CLL14 trial. This chart shows the incidences during VEN+G combination therapy, during single-agent VENCLEXTA treatment, as well as when the patients were off treatment. Neutropenia was the most common Grade 3 or 4 adverse reaction. Therefore, I monitor complete blood counts throughout the treatment period. I hold the VENCLEXTA dose for severe neutropenia and resume at the same or a reduced dose depending on how many times the neutropenia has occurred. I also consider supportive measures, including antimicrobials and G-CSF.

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Tumor lysis syndrome incidence in the CLL14 trial³

1% Laboratory TLS
0% Clinical TLS

The incidence of laboratory TLS was 1% (3/212) in patients treated with VEN+G. All 3 events of TLS occurred during treatment with GAZYVA^® (obinutuzumab), before treatment initiation with VENCLEXTA. All 3 events of TLS resolved and did not lead to withdrawal from the trial. GAZYVA administration was delayed in 2 cases in response to the TLS events
The incidence of clinical TLS was 0%

Dr. Saba:
Another consideration for all my patients is tumor lysis syndrome, which is an important identified risk with VENCLEXTA. In the CLL14 trial, the incidence of laboratory TLS was 1% (3/212) in patients treated with VEN+G.

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Managing Tumor Lysis Syndrome (TLS)³

VENCLEXTA can cause rapid reductions in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients and during reinitiation after dosage interruption in patients with CLL/SLL
Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase
TLS prophylaxis and monitoring protocols can reduce the risk of TLS
The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS

Dr. Saba:
It’s important to remember that TLS prophylaxis and monitoring protocols can reduce the risk of TLS with VENCLEXTA regimens, and the 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden, or debulk, and decrease the risk of TLS. The dosing guide for VENCLEXTA provided all of the information my staff and I needed for the dose ramp-up and beyond.

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CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS

OOP=out of pocket.

Dr. Saba:
The main reason I choose VENCLEXTA for the treatment of CLL is its fixed-duration strategy. This allows patients to go off treatment, at the same time allowing them to have a sustained PFS. For all these reasons, including proven efficacy, well-studied safety, a chance for time off treatment, and no ongoing out-of-pocket costs, VENCLEXTA regimens are my first choice for patients like Cheryl.

ISI Voiceover/TEXT ON SCREEN:
Important Safety Information

Contraindication

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.
VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase. TLS, including fatal cases, has been reported after a single 20 mg dose.
In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

Immunization

Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective.

Embryo-Fetal Toxicity

VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

Adverse Reactions

In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

Drug Interactions

Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.
Avoid concomitant use of strong or moderate CYP3A inducers.
Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.

Lactation

Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

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References

1. Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patients with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Blood. 2021;138(Suppl1):1927-1929. 2. Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patients with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Poster presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021. 3. VENCLEXTA Prescribing Information. 4. AI-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Abstract presented at the European Hematology Association Congress 2023; June 8-11, 2023. 5. Data on fileJ AbbVie Inc. 6-year data ABVRRT 176226. 6. Fischer K, AI-Sawaf O, Bahia J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines.) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. V.2.2023. National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13J 2023. To view the most recent and complete version of the guidelines, go online to NCCN.org

VENCLEXTA^® and its design are registered trademarks of AbbVie Inc. GAZYVA^® is a registered trademark of Genentech, Inc.

PFS during treatment-free period

Dr. Bita Fakhri discusses the benefits of choosing a fixed-duration therapy with time off treatment, durable progression-free survival (PFS), and outcomes during the treatment-free period.

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TEXT ON SCREEN:
VENCLEXTA CLL Portraits: A look at CLL patients and the doctors who treat them

Featuring Dr. Bita Fakhri Assistant Professor of Medicine in the Division of Hematology at Stanford Medical Center

Hypothetical patient profile. All patients and their results are different.

TEXT ON SCREEN:
Disclaimers:

This video is sponsored by AbbVie and Genentech, Inc., a member of the Roche Group
The healthcare provider included in this video is presenting information on behalf of AbbVie and Genentech, Inc., a member of the Roche Group

TEXT ON SCREEN:
Dr. Bita Fakhri Assistant professor of Medicine in the Division of Hematology at Stanford Medical Center

Dr. Fakhri:
Hi, I’m Doctor Bita Fakhri, Assistant Professor of Medicine in the Division of Hematology at Stanford Medical Center. Today I’d like to share a hypothetical CLL patient profile and discuss some of the factors that help me choose a treatment for my own patients.

TEXT ON SCREEN:
George, 72 years old Patient with previously untreated chronic lymphocytic leukemia (CLL)

Hypothetical patient profile. All patients and their results are different.

Actor Portrayal

Dr. Fakhri:
George is a type of patient that I am very familiar with from my practice. I’ve had a good amount of experience using VENCLEXTA plus GAZYVA in patients like George who have previously untreated CLL.

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Comorbidities: Arthritis, obesity, diabetes mellitus (type 2)

ECOG PS: 1
CIRS: 9
Prognostic Risk Factors: Unmutated IGHV; no 17p deletion
ECOG=Eastern Cooperative Oncology Group; PS=performance status; CIRS=cumulative illness rating scale; IGHV=immunoglobulin heavy-chain variable gene

Hypothetical patient profile. All patients and their results are different.

Dr. Fakhri:
George is 72 years old and his comorbidities include arthritis, obesity, and type 2 diabetes mellitus. You can see the rest of his clinical background here. Considering this profile, I know I have different treatment options to choose for a patient like George. That’s why I consider the clinical profile as well as other factors, like his preference for a treatment that will best fit his lifestyle.

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Over 3 out of 4 respondents preferred finite-duration therapy

CLL Society Patient Preference Survey (2021)^1,2

The survey was not designed to measure preference for venetoclax fixed-duration regimens.

When 608 patients and 22 caregivers were asked about preference for duration of CLL therapy, if effectiveness and side effects were assumed similar:

77% preferred finite-duration therapy
7% preferred continuous therapy*

Until disease progression or intolerance.

uMRD=undetectable minimal residual disease.

Survey question results:

77% preferred finite-duration therapy, which includes:
- 63% who responded "Limited duration therapy that is stopped after reaching uMRD or preplanned period of time if uMRD is not reached"
- 14% who responded "Limited duration therapy that is stopped after a preplanned period of time
10% No preference for the duration of therapy
7% Therapy that is taken indefinitely
6% Don't know/not sure

Limitations include the opt-in sample where the survey results may not be reflective of the general CLL population and their caregivers.

Dr. Fakhri:
This is something that my patients bring up to me often. In George’s case, his profile reminds me of a recent survey from the CLL Society. Although the survey is not related to any particular therapy, it showed that a majority of patients preferred a finite-duration therapy. I think it’s important to take patient preferences into account.

Looking at all aspects of George’s profile, I would strongly consider VENCLEXTA plus GAZYVA due to this regimen’s proven efficacy and safety. This regimen offers a chance for durable progression-free survival without continuous treatment. For a patient like George, this means a chance to get back to a life without a daily reminder of his treatment and disease.

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VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia

Continue viewing this video for Important Safety Information at the end of this video.

Dr. Fakhri:
VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Continue viewing for Important Safety Information at the end of the video.

Dr. Fakhri:
Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment.

TEXT ON SCREEN:
Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment.

Dr. Fakhri:
Warnings and precautions include tumor lysis syndrome, neutropenia, infections, immunization, embryo-fetal toxicity, and increased mortality in patients with multiple myeloma when VENCLEXTA is added to bortezomib and dexamethasone.

Appropriate precautions should be taken by the healthcare provider.

TEXT ON SCREEN:

Dr. Bita Fakhri Assistant Professor of Medicine in the Division of Hematology at Stanford Medical Center

Dr. Fakhri:
VENCLEXTA regimens offer my patients proven efficacy and a well-studied safety profile.

TEXT ON SCREEN:
CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS

OOP=out of pocket

Dr. Fakhri:
VENCLEXTA regimens offer patients the chance for time off treatment and no ongoing treatment exposure.

Let’s review some additional VENCLEXTA data in patients like George.

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1L CLL PATIENTS (N=432)

RANDOMIZED 1:1

GAZYVA^® (obinutuzumab) IV x 6 cycles
Chlorambucil oral x 12 cycles
GAZYVA IV x 6 cycles

TREATMENT COMPLETE AFTER 1 YEAR
Graphic not to scale.

CLL14 was a multicenter, open-label, actively controlled phase 3 trial (randomized 1:1)^3,4
In CLL14, the VEN+G regimen was designed to be completed after 12 months (twelve 28-day treatment cycles):
- GAZYVA IV infusion was administered at 1000 mg on Days 1 (the first dose could be split as 100 mg and 900 mg on Days 1 and 2, respectively), 8 and 15 of Cycle 1, and on Day 1 of each subsequent cycle for a total of 6 cycles³
- VENCLEXTA oral tablets were administered according to the 5-week dose ramp-up schedule: 20 mg daily during Cycle 1, Days 22-28; 50 mg daily during Cycle 2, Days 1-7; 100 mg daily during Cycle 2, Days 8-14; 200 mg daily during Cycle 2, Days 15-21; 400 mg daily during Cycle 2. Days 22-28 and on Days 1-28 of all subsequent cycles until the end of Cycle 12³
- In the GClb arm of CLL14, GAZYVA was administered in Cycles 1-6; chlorambucil was administered at 0.5 mg/kg orally on Day 1 and Day 15 of Cycles 1 to 12³

1L=first-line; IV=intravenous; VEN+G=VENCLEXTA + GAZYVA; GClb=GAZYVA + chlorambucil.

Dr. Fakhri:
With fixed-duration VENCLEXTA regimens, I can give patients like George the chance for durable progression-free survival, or PFS, without continuous treatment. This is based on the pivotal CLL14 trial, which studied VENCLEXTA + GAZYVA, or VEN+G, in the treatment of previously untreated patients.

CLL14 was a multicenter, randomized, open-label, phase 3 trial that evaluated 1 year of fixed treatment with VEN+G vs GAZYVA plus chlorambucil, or GClb, in patients with previously untreated CLL.

TEXT ON SCREEN:
CLL14 trial design: a randomized clinical trial of 432 patients
(VEN+G: N=216; GClb: N=216) with previously untreated CLL.³

IRC-assessed PFS (primary endpoint)³

67% reduction in risk of progression or death vs GClb (HR=0.33; 95% Cl: 0.22-0.51 [P<0.0001])

After a median follow-up of 28 months (range: 0-36 months):

There were 29 events in the VEN+G arm (14 progressions and 15 deaths without disease progression) compared with 79 events in the GClb arm (71 progressions and 8 deaths without disease progression)^*
Median PFS was not reached in either arm

^*Number of events based on earliest event of disease progression or deaths without disease progression due to any cause.

IRC=independent review committee; PFS=progression-free survival; HR=hazard ratio; Cl=confidence interval.

Dr. Fakhri:
In CLL14, VEN+G demonstrated durable PFS without long-term treatment.
VEN+G reduced the risk of disease progression or death without disease progression by 67% vs GClb. Median progression-free survival was not reached in either arm.

TEXT ON SCREEN:
[6-YEAR FOLLOW-UP ANALYSIS OF INV-ASSESSED PFS TABLE]

6-year follow-up analysis of INV-assessed PFS (overall follow-up of 86.5 months)^5*

PFS estimates may be unreliable at the tall end of the curve due to smaller number of patients at risk

*Based on data as of clinical data cutoff date of November 14, 2022; time of analysis was not pre-specified.
INV=investigator; TTNT=time to next treatment.

The PFS and TTNT follow-up analyses were not tested for statistical significance⁵

With a median follow-up of 76.4 months (range: 0-86.5 months), median PFS was estimated to be 76.2 months (95% Cl: 65.1-83.3) for the VEN+G arm and 36.4 months (95% Cl: 34.1-41.0) in the GClb arm (HR=0.40; 95% Cl: 0.31-0.52)
Of the 101 events in the VEN+G arm, 67 were disease progression, and 34 were deaths without disease progression. Of the 161 events in the GClb arm, 141 were disease progression, and 20 were deaths without disease progression

Dr. Fakhri:
The estimated 6-year progression-free survival rate was 53% for VEN+G vs 22% for GClb. My impression of the long-term follow-up CLL14 trial in general is very positive. So we learned from the 6-year follow-up data that patients who took the combination of VENCLEXTA and GAZYVA for 1 year were off therapy for 5 years. Six-year PFS, or progression-free survival, was 53%. And in a 6-year follow-up analysis of time to next treatment, at the time of the analysis, 64% of patients in the VEN+G arm had not received subsequent treatment (vs 35% of patients in the GClb arm). That means 6 out of 10 patients still didn’t require the next line of therapy 5 years after completing first-line treatment with VEN+G, which is important to consider for a patient like George who is concerned about ongoing therapy.

TEXT ON SCREEN:
[ADVERSE REACTIONS BY BODY SYSTEM TABLE]

*Includes multiple adverse reaction terms.
VEN+G=VENCLEXTA+GAZYVA; GClb=GAZYVA+chlorambucil.

Dr. Fakhri:
I always discuss with my patients the risks associated with the VENCLEXTA regimen. The most common adverse reactions in the CLL14 trial were neutropenia, diarrhea, and fatigue. Neutropenia was the most common Grade 3 or 4 adverse reaction. Therefore, I monitor complete blood counts throughout the treatment period. I hold the VENCLEXTA dose for severe neutropenia and resume at the same or a reduced dose depending on how many times the neutropenia has occurred. I also consider supportive measures, including antimicrobials and G-CSF.

TEXT ON SCREEN:
[GRADE 3/4 AEs GRAPHIC] (%)5*^†GRADE 3/4 AEs (%)⁵*^†

*Based on data as of clinical cutoff date of November 14, 2022.
"The chart reflects Grade 3/4 AEs with incidence ≥5%.
AE=adverse event; TLS=tumor lysis syndrome.

Dr. Fakhri:
Here we see grade 3 and 4 adverse events in addition to neutropenia that were seen in the CLL 14 trial with VEN+G. You can see the incidences during VEN+G combination therapy as well as during the single-agent VEN phase, and finally when patients were off treatment.

As you can see here this regimen allows me to limit my patients’ exposure as well as potential side effects after completing treatment, which is good for a patient like George, who is concerned about lengthy therapy.

TEXT ON SCREEN:
Tumor lysis syndrome incidence in the CLL14 trial³

1% Laboratory TLS
0% Clinical TLS

The incidence of laboratory TLS was 1% (3/212) in patients treated with VEN+G. All 3 events of TLS occurred during treatment with GAZYVA^® (obinutuzumab), before treatment initiation with VENCLEXTA. All 3 events of TLS resolved and did not lead to withdrawal from the trial. GAZYVA administration was delayed in 2 cases in response to the TLS events
The incidence of clinical TLS was 0%

Dr. Fakhri:
Another consideration for all my patients is tumor lysis syndrome, which is an important identified risk with VENCLEXTA. In the CLL14 trial, the incidence of laboratory TLS was 1% (3/212) in patients treated with VEN+G.

TEXT ON SCREEN:
Managing Tumor Lysis Syndrome (TLS)³

VENCLEXTA can cause rapid reductions in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients and during reinitiation after dosage interruption in patients with CLL/SLL
Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase
TLS prophylaxis and monitoring protocols can reduce the risk of TLS
The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS

Dr. Fakhri:
It’s important to remember that TLS prophylaxis and monitoring protocols can reduce the risk of TLS with VENCLEXTA regimens, and the 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden, or debulk, and decrease the risk of TLS. The dosing guide for VENCLEXTA provided the information my staff and I needed for the dose ramp-up and beyond.

TEXT ON SCREEN:
CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS

OOP=out of pocket

Dr. Fakhri:
I am heavily encouraged by the fact that this regimen was time limited, unlike some other very effective regimens that we have for patients with CLL, but they’re potentially lifelong, treat until progression. So the fact that CLL14 trial, combining VENCLEXTA with GAZYVA, provided the opportunity of time-limited therapy makes it a very appealing option for me to definitely discuss with patients who are considering treatment for their CLL.

ISI Voiceover:
Important Safety Information

Contraindication

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.
VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase. TLS, including fatal cases, has been reported after a single 20 mg dose.
In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

Immunization

Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective.

Embryo-Fetal Toxicity

VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

Adverse Reactions

In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

Drug Interactions

Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.
Avoid concomitant use of strong or moderate CYP3A inducers.
Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.

Lactation

Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

TEXT ON SCREEN:
References

1. Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patients with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Blood. 2021;138(Suppl1):1927-1929.

2. Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patients with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Poster presented at the: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021.

3. VENCLEXTA Prescribing Information.

4. Fischer K, AI-Sawaf O, Bahia J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.

5. Data on file, AbbVie Inc. 6-year data ABVRRTl76226.

Navigating comorbidities

Dr. Nakhle Saba discusses VENCLEXTA safety and use in patients with comorbidities, like cardiovascular disease.¹

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Open Transcript

TEXT ON SCREEN:
VENCLEXTA CLL Portraits: A look at CLL patients and the doctors who treat them

Featuring Dr. Nakhle Saba, Associate Professor of Medicine in Hematology-Oncology at Tulane University
Hypothetical patient profile All patients and their results are different.

TEXT ON SCREEN:
Disclaimers:

This video is sponsored by AbbVie and Genentech, Inc., a member of the Roche Group
The healthcare provider included in this video is presenting information on behalf of AbbVie and Genentech, Inc., a member of the Roche Group

TEXT ON SCREEN:
Dr. Nakhle Saba, Associate Professor of Medicine in Hematology-Oncology at Tulane University

PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION.

Hypothetical patient profile. All patients and their results are different.

Dr. Saba:
Hi, I’m Doctor Nakhle Saba, Associate Professor of Medicine in Hematology-Oncology at Tulane University. Today, I’d like to share a hypothetical CLL patient profile and discuss some of the factors that help me choose a treatment for my own patients.

My treatment decision varies by patient type. Like many other cancers, personalized medicine made its way to CLL. And by patient types, I mean the patient characteristics, disease risk stratification, patient’s age, patient comorbidities, and definitely, definitely patients’ preference.

TEXT ON SCREEN:
Martin, 82 years old
Patient with previously untreated chronic lymphocytic leukemia (CLL)

Dr. Saba:
Martin is a type of patient that I see quite often in my practice. I’ve had a good amount of experience using VENCLEXTA plus GAZYVA with patients like Martin who have previously untreated CLL.

When I consider treating a patient like Martin, I take a number of things into account. I’ll consider his age and his full clinical background, as well as how the treatment might affect his day-to-day life.

TEXT ON SCREEN:
Martin, 82 years old
Patient with previously untreated chronic lymphocytic leukemia (CLL)

Comorbidities: Hypertension; cardiovascular disease
ECOG PS: 2
CIRS: 9
Prognostic Risk Factors Unmutated IGHV, no 17p deletion

ECOG=Eastern Cooperative Oncology Group; PS=performance status; CIRS=cumulative illness rating scale; IGHV=immunoglobulin heavy-chain variable gene; PFS=progression-free survival.

Actor Portrayal

Dr. Saba:
Martin is 82 years old with comorbidities that include hypertension and cardiovascular disease. You can see the rest of his clinical background here. Looking at all aspects of his profile, I would strongly consider VENCLEXTA plus GAZYVA, or VEN+G, due to this regimen’s proven efficacy and safety. This regimen offers a chance for durable progression-free survival without continuous treatment, which can mean a patient like Martin has a chance to get back to a life without a daily reminder of his treatment and disease.

TEXT ON SCREEN
VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Continue viewing this video for Important Safety Information at the end of the video.

Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment.

Dr. Saba:

VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Continue viewing for Important Safety Information at the end of the video.

Serious and sometimes fatal adverse reactions occurred with VENCLEXTA treatment. Warnings and precautions include tumor lysis syndrome, neutropenia, infections, immunizations, embryo-fetal toxicity, and increased mortality in patients with multiple myeloma when VENCLEXTA is added to bortezomib and dexamethasone.

Appropriate precautions should be taken by the healthcare provider.

TEXT ON SCREEN:
Dr. Nakhle Saba, Associate Professor of Medicine in Hematology-Oncology at Tulane University

Dr. Saba:
VENCLEXTA regimens offer my patients proven efficacy and a well-studied safety profile.

TEXT ON SCREEN:
CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS

OOP=out of pocket

Dr. Saba:
VENCLEXTA regimens also offer patients the chance for time off treatment and no ongoing treatment exposure.

Another benefit is that there are no additional out-of-pocket costs with the VENCLEXTA regimen after the patient has completed treatment per the recommended dosing. This can be very important for a retired patient like Martin.

TEXT ON SCREEN:
[ADVERSE REACTIONS BY BODY SYSTEM TABLE]

*Includes multiple adverse reaction terms.
VEN+G=VENCLEXTA+GAZYVA; GClb=GAZYVA+chlorambucil.

Dr. Saba:

Considering Martin’s age, I am also encouraged that VENCLEXTA regimens have proven efficacy and a well-studied safety profile. I always discuss with my patients the risks associated with the VENCLEXTA regimen. The most common adverse reactions in the CLL14 trial were neutropenia, diarrhea, and fatigue.

TEXT ON SCREEN:
[GRADE 3/4 AEs GRAPHIC] (%)⁵*^†

GRADE 3/4 AEs (%)⁵*^†

Other important Grade 3/4 AEs
- Febrile neutropenia: 4% during combination-therapy period. 0% during single-agent period, 1% during off treatment period
- Pneumonia: 3% during combination-therapy period. 1% during single-agent period, 3% during off treatment period
- TLS: 1% during combination-therapy period, 0% during single-agent period, 0% during off treatment period
VEN+G combination-therapy period (6 cycles): Includes Grade 3 and 4 treatment-emergent AEs occurring on or before last exposure date of GAZYVA + 29 days
VENCLEXTA single-agent period (6 cycles): Includes Grade 3 and 4 AEs occurring after the start of the VEN monotherapy period to last date of VEN + 29 day
Off treatment: Includes Grade 3 and 4 AEs occurring after 29 days and up to 6 months after treatment completion
Multiple occurrences of the same AE in an individual during the same treatment period are counted only once for that treatment period

*Based on data as of clinical cutoff date of November 14, 2022.
^†The chart reflects Grade 3/4 AEs with incidence ≥5%.
AE=adverse event; TLS=tumor lysis syndrome.

Dr. Saba:
Here you see the incidence of Grade 3 and 4 adverse events from the 6-year follow-up of the CLL14 trial. This chart shows the incidences during VEN+G combination therapy, during single-agent VENCLEXTA treatment, as well as when the patients were off treatment. Neutropenia was the most common Grade 3 or 4 adverse reaction. Therefore, I monitor complete blood counts throughout the treatment period. I hold the VENCLEXTA dose for severe neutropenia and resume at the same or a reduced dose depending on how many times the neutropenia has occurred. I also consider supportive measures, including antimicrobials and G-CSF.

TEXT ON SCREEN:
Cardiovascular adverse events in patients treated with VEN+G^3*†[CARDIOVASCULAR ADVERSE EVENTS IN PATIENTS TREATED WITH VEN+G3 TABLE]

The analysis was not powered to demonstrate a statistically significant difference between VEN+G and GClb adverse events

*Based on data as of clinical data cutoff date of August 23, 2019.³Shown are Grade 3, 4, and 5 events with frequency 1% or higher and their corresponding Any Grade rates.^{3

‡}Includes multiple adverse reaction terms.³

Dr. Saba:
Martin has a history of hypertension and cardiovascular disease, which is why the additional data showing the cardiovascular safety profile in patients treated with VEN+G are important to consider.

I think VENCLEXTA plus GAZYVA is a very appropriate treatment for Martin for multiple reasons. His age, comorbidities, and risk stratification for his CLL were well represented in CLL14.

Dr. Saba:
For all these reasons, including proven efficacy, well-studied safety, a chance for time off treatment, and no ongoing out-of-pocket costs, a VENCLEXTA-based regimen is my first choice for patients like Martin.

TEXT ON SCREEN:
CLINICAL OUTCOMES
PATIENT EXPERIENCE
NO ONGOING OOP COSTS

OOP=out of pocket

ISI Voiceover/TEXT ON SCREEN:
Important Safety Information

Contraindication

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.
VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase. TLS, including fatal cases, has been reported after a single 20 mg dose.
In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

Immunization

Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective.

Embryo-Fetal Toxicity

VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

Adverse Reactions

In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

Drug Interactions

Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.
Avoid concomitant use of strong or moderate CYP3A inducers.
Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.

Lactation

Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

TEXT ON SCREEN:
References

1. VENCLEXTA Prescribing Information. 2. Data on file, AbbVle Inc. 6-year data ABVRRTl76226. 3. Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzurnab versus chlorarmbuciI plus obinutuzurnab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomized, phase 3 trial. Lancet Oncol. 2020;21(9);1188-1200.

Starting VENCLEXTA

Christina Patterson, PA-C, explains how to assess, prepare, and initiate VENCLEXTA in patients with previously untreated and R/R CLL.

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Open Transcript

Text on Screen: Patient Initiation Treatment With VENCLEXTA^® (venetoclax tablets) Regimens

Christina Patterson, PA-C

Cancer Care Associates of York

York, PA

US-VENC-220202

PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION ON THIS WEBSITE

Text on Screen: Disclaimer

This video is sponsored by AbbVie and Genentech, Inc., a member of the Roche Group.
The healthcare provider included in this video is presenting information on behalf of AbbVie and Genentech, Inc., a member of the Roche group.

Text on Screen:

Christina Patterson, PA-C

Cancer Care Associates of York

York, PA

Christina:

Hello, my name is Christina Patterson and I am a physician assistant practicing at Cancer Care Associates of York in York, Pennsylvania
Welcome to the VENCLEXTA patient initiation video for patients with previously untreated or relapsed, refractory chronic lymphocytic leukemia or CLL
Each year, I work with around 40 patients with CLL in our community oncology practice who are being treated with VENCLEXTA
My goal is to share our experiences with VENCLEXTA and, in particular, the preparations and planning that we do when initiating treatment

Text on Screen: Indication in CLL

VENCLEXTA is a BCL-2 inhibitor indicated¹:

For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

Christina:

It is important to note that VENCLEXTA is a BCL-2 inhibitor that is indicated for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma

Text on Screen: Select Important Safety Information

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).
Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA. The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increase venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.
Grade 3 or 4 neutropenia occurred in patients treated with VENCLEXTA. Monitor complete blood counts and for signs of infection; manage as medically appropriate.
Fatal and serious infections such as pneumonia and sepsis have occurred in patients with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 or 4 infection until resolution.
Do not administer live attenuated vaccines prior to, during, or after treatment until B-cell recovery occurs.
VENCLEXTA may cause embryo-fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose.

Text on Screen: PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION ON THIS WEBSITE.

Christina:

In my experience, I find that the best way to be successful with VENCLEXTA is to educate your team and your patients, and to have a plan in place before treatment even begins

Text on Screen: The dose ramp-up was designed to gradually debulk tumor burden and decrease the risk of TLS¹

Christina:

The dosing schedules shown here were specifically designed to initiate treatment with VENCLEXTA to help reduce tumor burden in the debulking phase and decrease the risk of TLS
Regardless of the line of treatment in CLL, VENCLEXTA dosing ramps up over a period of 5 weeks
In the first week of treatment, the patients will receive 20 mg per day of VENCLEXTA orally. The dose will increase weekly to 50, 100, 200, and eventually 400 mg per day
We explain to our patients that because of how VENCLEXTA works, we need to gradually ramp-up dosing, and apply prophylaxis and appropriate monitoring
Upon completion of the 5-week ramp-up, we’ll continue dosing at 400 mg per day until the end of the prescribed treatment regimen, unless VENCLEXTA delay, decrease, or discontinuation is required

Text on Screen: PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION ON THIS WEBSITE.

Christina:

When your patient has been prescribed VENCLEXTA, you should ensure that the VENCLEXTA Starting Pack is ordered
The starter pack was designed to facilitate dosing according to the ramp-up schedule for weeks 1 through 4 with weekly, color-coded, wallet blister packs. The dosing for Week 5 onwards is provided to the patient in a bottle
To order, please contact your specialty distributor. A list can be found on www.venclextahcp.com

Text on Screen: Initiating VENCLEXTA with GAZYVA^® (Obinutuzumab) or rituximab

STEP 1: ASSESS prior to VENCLEXTA
STEP 2: PREPARE at least 2 days prior to first dose
STEP 3: INITIATE 5-week VENCLEXTA ramp-up

Christina:

Let's take a closer look at how we should initiate treatment
To that end, there are 3 key steps to this process
It starts with assessing tumor burden
Then, preparing for the first dose of VENCLEXTA
And finally, initiating VENCLEXTA treatment with the dose ramp-up protocol
I’d like to emphasize that these steps are the same, regardless of whether your patients are receiving VENCLEXTA with an anti-CD20 monoclonal antibody or as monotherapy

Text on Screen: Considerations for TLS with VENCLEXTA¹

VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at the initial 5-week ramp-up phase in all patients, and during reinitiation after dosage interruption
Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function (CrCl <80 mL/min) and tumor burden; splenomegaly may also increase the risk

Christina:

In order to prepare our team prior to treatment with VENCLEXTA, I sit down with our nurses and schedulers and, based on a patient’s tumor burden and other clinical characteristics, we will adjust their monitoring and labs to ensure that we are giving our patients the tailored care that they need

Text on Screen: Considerations for TLS with VENCLEXTA¹

Consider all patient comorbidities before final determination of prophylaxis and monitoring schedule
The risk of TLS may decrease as tumor burden decreases
Reassess the risk of TLS when reinitiating VENCLEXTA after a dosage interruption lasting more than 1 week during the ramp-up phase, or more than 2 weeks after completion of ramp-up. Institute prophylaxis and monitoring as needed

Appropriate prophylaxis can help lower the risk of TLS.

Assess Blood Chemistry and Correct Pre-existing Abnormalities Prior to Initiation of Treatment:

Potassium
Uric acid
Phosphorus
Calcium
Creatinine

Christina:

In the past we have reached out to our patient advocates at our center for help on various challenges
Planning the treatment out doesn’t end with the logistics, however, as it requires that both our staff and our patients know and understand every part of the treatment process—essentially why we are doing what we are doing

Text on Screen: Patients With Low or Medium Tumor Burden May Be Initiated in the Outpatient Setting¹

Consider all patient comorbidities before final determination of prophylaxis and monitoring schedule
Patients who may be initiated in the outpatient setting:
- Low tumor burden: those with all lymph nodes (LN) <5 cm and an absolute lymphocyte count (ALC) <25 x 10⁹/L
- Medium tumor burden: those with any LN from 5 cm to <10 cm or an ALC ≥25 x 10⁹/L
For the first dose of 20 mg and 50 mg, consider hospitalization for patients with medium tumor burden and CrCl <80 mL/min

Christina:

Note that, depending on the assessed tumor burden, I may be administering the initial 20 mg and 50 mg doses of VENCLEXTA in the outpatient or the hospital setting with the related lab monitoring
From our experience, some patients will need to be in the hospital initially
To put this into perspective, in the CLL14 study in the first-line setting, 22% of patients were characterized as having a high risk of TLS, which would have necessitated an in-hospital start with VENCLEXTA

Text on Screen: Patients With Low or Medium Tumor Burden May Be Initiated in the Outpatient Setting^1,3

Patients with high tumor burden—those with an LN ≥10 cm or those with ALC ≥25 x 10⁹/L and any LN ≥5 cm—should be initiated in the hospital¹
In the CLL14 trial, TLS risk category was chosen based on investigator discretion, LN size, and ALC^1,3
- Baseline characteristics in the CLL14 trial: 13% (29/216) of VEN+G patients had low, 64% (139/216) had medium, and 22% (48/216) had high TLS risk²

Christina:

The majority of patients in CLL14 were characterized as having a low or medium risk of TLS, and thus this majority could start VENCLEXTA and be managed in an outpatient setting, unless other factors, such as comorbidities, suggest the patient should initiate VENCLEXTA in the hospital setting
Starting in the hospital requires a slightly different focus for patients and nurses than when it is done in the outpatient setting
One way we have improved the logistics of the onboarding is that we have worked with our electronic medical records to design VENCLEXTA order sets based on Prescribing Information and our experience

Text on Screen: It is important to go over the Medication Guide with the patient.

Christina:

We stress to them the importance of hydration, particularly during the dose ramp-up period. I would say this is a really important thing that patients have control over in making treatment initiation a success
We give each patient a specific outline for the dates to begin taking allopurinol and start the hydration protocol. We will also specify the dates and times of each dose, as well as the dates and times for their lab work and related follow-up appointments
By having the days of the week and appointments filled in ahead of time, patients can actually be marking off when things have been completed and track their progress through ramp-up
This can help make things as simple as possible for our patients
Please see the full Prescribing Information for complete preparation recommendations
Our schedulers need to understand the timing behind when we need our patients to get labs and how this will impact their appointment time

Text on Screen: Plan Ahead for Labs¹

Evaluate blood chemistries (potassium, uric acid, phosphorous, calcium, and creatinine)
Review in real time

Christina:

Thus, patients and their providers understand that, while it may seem like there is a lot of upfront monitoring and labs during VENCLEXTA initiation, that is simply part of the process
It is important to plan ahead for labs to make sure patients are appropriately monitored

Text on Screen: Plan Ahead for Labs¹

Evaluate blood chemistries (potassium, uric acid, phosphorous, calcium, and creatinine)
Review in real time

Christina:

A few ways to get stat labs are: To get them in your own outpatient clinic, which is what we do. Another option might be to get stat labs in a local or affiliated outpatient hospital. Another common option could be to get them at a local or national reference lab
What’s important is that the lab understands why you need a response quickly

Text on Screen: PLEASE SEE IMPORTANT SAFETY INFORMATION AT THE END OF THIS VIDEO AND FULL PRESCRIBING INFORMATION ON THIS WEBSITE.

Christina:

Ultimately, the treatment initiation for the VENCLEXTA regimen requires some planning for you and your patient
My biggest piece of advice with VENCLEXTA is to educate your team, educate your patients, and simply be prepared
In my opinion, both academic centers and community practices should be able to successfully initiate VENCLEXTA
Thank you for taking the time to walk with me through the initiation of treatment with VENCLEXTA for patients with previously untreated or relapsed, refractory CLL

Text on Screen: [ISI]

References:

VENCLEXTA Prescribing Information.
Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236 (suppl appendix).

VO: Please see accompanying full Prescribing Information.

Text on Screen: This presentation is by [AbbVie logo] [Genentech logo]

VO: This video has been presented on behalf of AbbVie and Genentech.

US-VENC-220202

CLL=chronic lymphocytic leukemia; R/R=relapsed/refractory.

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US-VENC-230235

Indication

VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Important Safety Information

Contraindication

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.
VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase. TLS, including fatal cases, has been reported after a single 20 mg dose.
In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

Immunization

Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective.

Embryo-Fetal Toxicity

VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

Adverse Reactions

In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

Drug Interactions

Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.
Avoid concomitant use of strong or moderate CYP3A inducers.
Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.

Lactation

Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

Please see full Prescribing Information.

VENCLEXTA^® and its design are registered trademarks of AbbVie Inc.
GAZYVA^® is a registered trademark of Genentech, Inc.

- VENCLEXTA Prescribing Information.
  
  VENCLEXTA Prescribing Information.
- Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
  
  Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
- GAZYVA Prescribing Information.
  
  GAZYVA Prescribing Information.
- Data on file, AbbVie Inc. ABVRRTI69608.
  
  Data on file, AbbVie Inc. ABVRRTI69608.
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  Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23)(suppl):2225-2236.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
- Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.
  
  Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.
- Data on file, AbbVie Inc. ABVRRTI69609.
  
  Data on file, AbbVie Inc. ABVRRTI69609.
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- Data on file, AbbVie Inc. ABVRRTI74115.
  
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