Venetoclax Combination Therapy for Relapsed or Refractory Multiple Myeloma
The novel combination of venetoclax plus bortezomib and dexamethasone demonstrated promising efficacy with an acceptable safety profile in patients with relapsed or refractory multiple myeloma, according to Philippe Moreau, MD, of the University Hospital of Nantes, France, and colleagues, who published their findings in Blood.
Antiapoptotic proteins BCL-2 and myeloid cell leukemia sequence 1 (MCL-1) promote multiple myeloma cell survival. Venetoclax (formerly known as ABT-199) is a selective, orally bioavailable small-molecule BCL-2 inhibitor, and bortezomib can indirectly inhibit MCL-1.
The phase Ib study (ClinicalTrials.gov identifier NCT01794507) enrolled 66 patients, with a median of 3 prior lines of treatment. Patients received daily venetoclax in combination with bortezomib and dexamethasone.
The overall response rate with the combination therapy was 67%, and 42% of patients achieved a very good partial response or better. The median time to disease progression and the duration of response were 9.5 and 9.7 months, respectively.
The treatment combination was also generally well tolerated. Gastrointestinal toxicities were common but low grade, and grade 3/4 adverse events reflected mainly myelosuppression.
Notably, patients with higher BCL-2 expression seemed to have the best responses to the combination, with an overall response rate of 94%, compared with 59% in patients with low BCL-2 expression, the investigators revealed.