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Updates in CLL Treatment: 5-Year Off Treatment Analyses of the CLL14 and MURANO Trials

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Join us as we examine the long-term data from two clinical studies that assessed a fixed-treatment regimen for chronic lymphocytic leukemia.

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  • Overview

    In the summer of 2023, researchers presented the long-term data updates from two trials studying a fixed-duration venetoclax regimen for the treatment of chronic lymphocytic leukemia (CLL). Joining Dr. Jennifer Caudle to examine the six-year data update from the CLL14 trial and seven-year final analysis of the MURANO study is Dr. Joanna Rhodes, Director of Lymphoma at Rutgers Cancer Institute of New Jersey in New Brunswick, New Jersey.

  • VENETOCLAX Indication and Safety Overview

    Indication

    •VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX.
    •VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENETOCLAX 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.
     

    Tumor Lysis Syndrome (continued)

    •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 VENETOCLAX follow dose modification guidance in the Prescribing Information.
    •Concomitant use of VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENETOCLAX 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 VENETOCLAX until B-cell recovery occurs. Advise patients that vaccinations may be less effective.
     

    Embryo-Fetal Toxicity

    •VENETOCLAX 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 VENETOCLAX is Added to Bortezomib and Dexamethasone

    •In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENETOCLAX to bortezomib plus dexamethasone, a use for which VENETOCLAX is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX 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 VENETOCLAX exposure, which may increase VENETOCLAX toxicities, including the risk of TLS. Consider alternative medications or adjust VENETOCLAX dosage and monitor more frequently for adverse reactions. Resume the VENETOCLAX 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 VENETOCLAX with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENETOCLAX.

    Lactation

    •Advise women not to breastfeed during treatment with VENETOCLAX 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 VENETOCLAX and for 30 days after the last dose.
    •Based on findings in animals, VENETOCLAX may impair male fertility.

    Hepatic Impairment

    •Reduce the dose of VENETOCLAX 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.
     
    Review full prescribing information for additional information at www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110 or go to abbviemedinfo.com.

    BCL2-US-00077-MC
      Version 1.0 Approved January 2024

Schedule28 Feb 2024