For Patients and Caregivers
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
See PFS Data*
Acute Myeloid Leukemia (AML)
See OS Data†

It is not known if VENCLEXTA is safe and effective in children. Actor portrayals.

(US-VEN-250149)


*Here are the three CLL regimens: The VEN+A regimen is designed to be completed after 12 cycles (twelve 28-day treatment cycles), preceded by a 2-cycle acalabrutinib initiation phase. Acalabrutinib is taken orally 100 mg approximately every 12 hours starting on Cycle 1, Day 1, for a total of 14 cycles or until disease progression or unacceptable toxicity. VENCLEXTA is taken orally 400 mg/day until disease progression, unacceptable toxicity, or for a total of 12 cycles after the 2-cycle acalabrutinib initiation phase, starting with the 5-week VENCLEXTA dose ramp-up schedule. AMPLIFY was a randomized, multicenter, open-label trial in patients with previously untreated CLL without TP53 mutation or 17p deletion (VEN+A: N=291; CIT: N=290) and with a median follow-up of 42.6 months (range: 1-59 months) in the VEN+A arm. VEN+A reduced the risk of progression or death by 35% vs CIT (HR=0.65; 95% CI: 0.49-0.87 [P<0.0038]). Median PFS was NR with VEN+A vs 47.6 months with CIT (95% CI: 43.3-NR).

The VEN+G regimen is designed to be completed after 12 months (twelve 28-day treatment cycles): GAZYVA® (obinutuzumab) is administered in Cycles 1-6, and VENCLEXTA is taken orally 400 mg/day from Cycle 3, Day 1, after the first 2 cycles of GAZYVA and the 5-week VENCLEXTA dose ramp-up. CLL14 was a randomized clinical trial of 432 patients (VEN+G: N=216; GClb: N=216) with previously untreated CLL and with a median follow-up of 28 months (range: 0-36 months). VEN+G reduced the risk of progression or death by 67% vs GCIb (HR=0.33; 95% CI: 0.22-0.51 [P<0.0001]). Median PFS was not reached in either arm.

The VEN+R regimen is designed to be completed after 24 months (twenty-four 28-day treatment cycles after the 5-week VENCLEXTA dose ramp-up): rituximab is administered in Cycles 1-6; VENCLEXTA is taken 400 mg/day orally from Cycle 1, Day 1 of rituximab through Cycle 24. MURANO was a randomized clinical trial of 389 patients (VEN+R: N=194; BR: N=195) with previously treated CLL and with a median follow-up of 23.4 months (range: 0-37.4+ months). VEN+R reduced the risk of progression or death by 81% vs BR (HR=0.19; 95% CI: 0.13-0.28 [P<0.0001]). Median PFS was not reached with VEN+R vs 18.1 months with BR (95% CI: 15.8-22.3).1

†VIALE-A was a randomized (2:1), double-blind, placebo-controlled, multicenter, phase 3 study that evaluated the efficacy and safety of VENCLEXTA in combination with azacitidine (VEN+AZA; N=286) vs placebo with azacitidine (PBO+AZA; N=145) in adults with newly diagnosed AML who were ≥75 years of age, or with comorbidities that precluded the use of intensive induction chemotherapy. The primary endpoint was OS. VEN+AZA improved survival vs AZA: median OS was 14.7 months with VEN+A (95% CI: 11.9-18.7) vs 9.6 months with AZA (95% CI: 7.4-12.7) (HR=0.66; 95% CI: 0.52-0.85 [P<0.001]).

AML=acute myeloid leukemia; AZA=azacitidine; BCL-2=B-cell lymphoma 2; BR=bendamustine-rituximab; CI=confidence interval; CIT=chemoimmunotherapy; CLL=chronic lymphocytic leukemia; FCR=fludarabine-cyclophosphamide-rituximab; GClb=GAZYVA + chlorambucil; HR=hazard ratio; NR=not reached; OS=overall survival; PBO+AZA=placebo + azacitidine; PFS=progression-free survival; TP53=tumor protein p53; VEN+A=VENCLEXTA + acalabrutinib; VEN+AZA=VENCLEXTA + azacitidine; VEN+G=VENCLEXTA + GAZYVA; VEN+R=VENCLEXTA + rituximab.

VENCLEXTA® (venetoclax tablets) is a selective BCL-2 inhibitor indicated for the treatment of adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML) in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, designed to help restore the process of apoptosis.1

In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.1 Learn more about the mechanism of action of VENCLEXTA. See detailed guidance on administration and dosing for CLL and administration and dosing for AML.

In CLL/SLL, the most common adverse reactions (≥20%) for VENCLEXTA when given in combination with obinutuzumab or rituximab or as monotherapy are neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema. The most common adverse reactions (≥20%) for VENCLEXTA when given in combination with acalabrutinib are neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19.1

In AML, the most common adverse reactions (≥30%) in combination with azacitidine or decitabine or low-dose cytarabine are nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.1

Initial US approval for CLL was April 2016 and AML was November 2018.1

Important Safety Information & Indications

Indications

VENCLEXTA is indicated:

  • For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
  • In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults:
    • 75 years or older, or
    • who have comorbidities that preclude use of intensive induction chemotherapy.

Important Safety Information

Contraindication
  • Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the 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.
  • In patients with AML who followed the current 3-day ramp-up dosing schedule and the TLS prophylaxis and monitoring measures, the rate of TLS was 1.1% in patients who received VENCLEXTA in combination with azacitidine. In patients with AML who followed a 4-day ramp-up dosing schedule and the TLS prophylaxis and monitoring measures, the rate of TLS was 5.6% and included deaths and renal failure in patients who received VENCLEXTA in combination with low-dose cytarabine.
  • 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 treated with VENCLEXTA in monotherapy and in combination studies with obinutuzumab or rituximab; febrile neutropenia occurred in 4% to 6% of patients. Grade 3 or 4 neutropenia developed in 38% of patients and Grade 4 neutropenia developed in 15% of patients when treated with VENCLEXTA in combination with acalabrutinib; febrile neutropenia occurred in 2% of patients.
  • In patients with AML, baseline neutrophil counts worsened in 95% to 100% of patients treated with VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine. Neutropenia can recur with subsequent cycles.
  • Monitor complete blood counts. Interrupt dosing for severe neutropenia. In CLL, resume at same or reduced dose. In AML, resume at same dose then reduce duration based on remission status and first or subsequent occurrence of neutropenia. 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.
  • In AMPLIFY, a randomized study in patients with previously untreated CLL/SLL, serious or Grade 3 or higher infections occurred in 14% of patients who received VENCLEXTA in combination with acalabrutinib (VEN+A), most commonly due to COVID-19; fatal infections occurred in 3.1% of patients.
  • In an additional cohort of patients receiving VENCLEXTA in combination with acalabrutinib and obinutuzumab (AVO) (an unapproved regimen for previously untreated CLL/SLL in AMPLIFY), serious or Grade 3 or higher infections occurred in 25%, most commonly due to COVID-19; fatal infections occurred in 6% of patients. The safety and effectiveness of AVO have not been established by the FDA in patients with previously untreated CLL/SLL.
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 acalabrutinib, serious adverse reactions were most often due to COVID-19 including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%). The most common adverse reactions (≥20%) of any grade were neutropenia (78%), headache (35%), diarrhea (33%), musculoskeletal pain (25%), and COVID-19 (21%). Fatal adverse reactions occurred in 3.4% of patients, most often from COVID-19 and COVID-19 pneumonia.
  • 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 AML receiving combination therapy with azacitidine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%), and hemorrhage (6%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were neutrophils decreased (98%), platelets decreased (94%), lymphocytes decreased (91%), hemoglobin decreased (61%), nausea (44%), diarrhea (43%), febrile neutropenia (42%), musculoskeletal pain (36%), pneumonia (33%), fatigue (31%), and vomiting (30%). Fatal adverse reactions occurred in 23% of patients who received VENCLEXTA in combination with azacitidine, with the most frequent (≥2%) being pneumonia (4%), sepsis (excluding fungal; 3%), and hemorrhage (2%).
  • In patients with AML receiving combination therapy with decitabine, the most frequent serious adverse reactions (≥10%) were sepsis (excluding fungal; 46%), febrile neutropenia (38%), and pneumonia (31%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were neutrophils decreased (100%), lymphocytes decreased (100%), white blood cells decreased (100%), platelets decreased (92%), hemoglobin decreased (69%), febrile neutropenia (69%), fatigue (62%), constipation (62%), musculoskeletal pain (54%), dizziness (54%), nausea (54%), abdominal pain (46%), diarrhea (46%), pneumonia (46%), sepsis (excluding fungal; 46%), cough (38%), pyrexia (31%), hypotension (31%), oropharyngeal pain (31%), edema (31%), and vomiting (31%). One (8%) fatal adverse reaction of bacteremia occurred within 30 days of starting treatment.
  • In patients with AML receiving combination therapy with low-dose cytarabine (LDAC), the most frequent serious adverse reactions (≥10%) were pneumonia (17%), febrile neutropenia (16%), and sepsis (excluding fungal; 12%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were platelets decreased (97%), neutrophils decreased (95%), lymphocytes decreased (92%), hemoglobin decreased (63%), nausea (42%), and febrile neutropenia (32%). Fatal adverse reactions occurred in 23% of patients who received VENCLEXTA in combination with LDAC, with the most frequent (≥5%) being pneumonia (6%) and sepsis (excluding fungal; 7%).
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. Concomitant use with a strong CYP3A inhibitor at initiation and during ramp-up phase in patients with CLL/SLL is contraindicated. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions in patients taking a steady daily dosage (after ramp-up phase). In patients with AML, 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 nursing 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.

    • VENCLEXTA Prescribing Information.

      VENCLEXTA Prescribing Information.

    +