The Food and Drug Administration (FDA) has placed a partial hold on all clinical trials evaluating venetoclax (Venclexta; AbbVie and Genentech) for the treatment of multiple myeloma. This was prompted after a review of data from the phase 3 BELLINI trial (M14-031) showed a higher proportion of deaths in the venetoclax treatment arm compared with the control arm in patients with relapsed/refractory multiple myeloma.
In the BELLINI trial, patients were randomized to receive venetoclax or placebo in combination with bortezomib and dexamethasone. Results showed that the study met its primary endpoint of progression-free survival (22.4 months vs 11.5 months), with statistically significant improvements in overall response rate (82% vs 68%) and very good partial response or better in the venetoclax arm vs control arm.
In the venetoclax arm, 13 of the 41 deaths were observed to be treatment-emergent (hazard ratio [HR] 2.03, 95% CI, 1.042–3.945); treatment-emergent deaths were due to infection (8/13) or refractory or progressive disease. In contrast, death occurred in 11.3% (11/97) of the placebo arm, of which 1.0% (1/11) was treatment-emergent.
Severe toxicity (Grade 3–5) incidence was similar between the venetoclax and placebo arms (86.5% and 87.5%, respectively) as were serious adverse events (48.2% vs 50.0%). Infections occurred in 79.8% and 77.1% of the venetoclax and placebo arms, respectively; pneumonia was seen in 20.7% and 15.6%, respectively.
As a result of the partial clinical hold, no new patients will be enrolled in any of the studies of venetoclax for multiple myeloma until additional analysis is conducted. Patients currently enrolled may continue treatment if it appears to be beneficial and after consultation with their physician.
Venclexta, a B-cell lymphoma-2 (BCL-2) inhibitor, is currently approved to treat chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, in patients who have received at least 1 prior therapy, alone or in combination with rituximab. It is also indicated for newly-diagnosed acute myeloid leukemia (AML) in adults aged ≥75 years or in those who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, or decitabine, or low-dose cytarabine.
For more information call (800) 633-9110 or visit Venclexta.com.