The U.S. Food and Drug Administration (FDA) has approved the combination of Venclexta (venetoclax) and acalabrutinib for the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL), AbbVie announced. The approval is based on results from the Phase 3 AMPLIFY trial.
The decision establishes the regimen as the first all-oral, fixed-duration combination therapy approved in the first-line setting for CLL. The treatment is designed to provide a time-limited alternative to continuous therapy, offering patients the potential for treatment-free intervals.
CLL is one of the most common types of leukemia in adults and originates in the bone marrow, affecting a subset of white blood cells known as lymphocytes. Although treatment outcomes have improved in recent years, many patients require prolonged therapy and ongoing disease management.
The global, multi-center Phase 3 AMPLIFY trial evaluated venetoclax plus acalabrutinib, with or without obinutuzumab, compared with investigator-selected chemoimmunotherapy regimens — fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine and rituximab (BR) — in patients without del(17p) or TP53 mutation. The venetoclax–acalabrutinib combination was administered for 14 cycles of 28 days each.
Trial results showed that the fixed-duration combination reduced the risk of disease progression or death by 35% compared with chemoimmunotherapy (hazard ratio 0.65; 95% CI: 0.49–0.87; p=0.0038). Median progression-free survival was not reached in the combination arm, compared with 47.6 months for chemoimmunotherapy.
The safety profile of the combination was consistent with the known safety profiles of the individual agents. The most common adverse reactions occurring in at least 20% of patients included neutropenia, headache, diarrhea, musculoskeletal pain and COVID-19. The most common serious adverse events included COVID-19, second primary malignancies and neutropenia. The incidence of tumor lysis syndrome was 0.3%, and no new safety signals were reported.
Venclexta is a B-cell lymphoma-2 (BCL-2) inhibitor that promotes cancer cell apoptosis by targeting a protein that helps malignant cells survive. The drug is jointly developed by AbbVie and Roche and is approved in more than 80 countries for various hematologic malignancies.
The supplemental new drug application approval expands first-line treatment options for patients with CLL, particularly those seeking time-limited oral regimens as an alternative to traditional chemo-immunotherapy.
Also Read