FDA warns, however, about the possibility of TLS due to rapid tumor cell destruction.
The United States Food and Drug Administration (FDA) has announced the regular approval of venetoclax (Venclexta, AbbVie and Genentech) in combination with rituximab for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion in patients who have received at least one prior therapy.
The FDA had previously granted Breakthrough Therapy designation and priority review for venetoclax administered with rituximab. Now, based on the results of the MURANO trial, the combination treatment is available to patients.
MURANO was a multicenter, open-label trial that randomly assigned 389 patients to venetoclax plus rituximab, or bendamustine with rituximab. In the intervention arm, patients completed a 5-week ramp-up with venetoclax and then received venetoclax at a dosage of 400 mg once daily for 24 months, measured from the rituximab start date. Rituximab was also initiated after the venetoclax ramp-up, and administered for 6 cycles. Bendamustine plus rituximab was given for 6 cycles.
After a median follow-up of almost 2 years, median progression-free survival (PFS) was not reached in the intervention arm, compared with a PFS of 18.1 months for the bendamustine/rituximab arm. This translated to an 81% reduction in the risk of disease progression or death (hazard ratio [HR], 0.19; 95% CI, 0.13–0.28; P < .0001).
More than 90% of patients assigned to venetoclax responded to treatment, compared with 72% of patients in the bendamustine arm.
The most common adverse events that occurred in patients assigned to venetoclax plus rituximab were neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea. Grade 3 or 4 neutropenia occurred in 64% of patients, and grade 4 neutropenia in about one-third of patients. A little less than half (46%) of patients had serious adverse events, including infections in 21% of patients.
In patients assigned to bendamustine, adverse effects resulted in treatment discontinuation in 10% of patients, dose reduction in 15%, and dose interruption in 40%. In patients assigned to venetoclax, adverse events led to dose interruption in 46% of patients, and discontinuation in 3%.
In its announcement of the approval, the FDA also warned about the possibility of tumor lysis syndrome (TLS) occurring due to the rapid destruction of tumor cells. Prescribing physicians should refer to the prescribing information for guidance on TLS risk stratification, prophylaxis, and monitoring.
According to the manufacturer, this combination is the first oral-based, chemotherapy-free combination treatment for CLL that allows patients an option for fixed treatment duration.
Venetoclax is also approved as a monotherapy for CLL with 17p deletion, as detected by an FDA-approved test, in patients who have received at least one prior therapy.