Venclexta (venetoclax) for multiple myeloma – pro
Venetoclax (Venclexta) in relapsed or refractory multiple myeloma improved most measures of response in the phase III BELLINI trial, yet an increased risk of early death prompted a partial hold from the FDA.
The study met its primary endpoint of improving median progression-free survival (PFS), at 22.4 months with the addition of venetoclax to bortezomib (Velcade) plus dexamethasone versus 11.5 months with the addition of placebo (HR 0.63, 95% CI 0.44-0.90, P=0.01).
What was surprising in this study was a decreased overall survival in the experimental arm, more deaths were observed in the venetoclax arm compared to the placebo arm. At a median follow-up of 18.7 months, 21% of patients in the investigational arm had died compared with 12% in the placebo arm (HR 2.03, 95% CI 1.04-3.95, P=0.034).
The majority of these deaths appeared to be related to infections in the context of progressive disease. y contrast, the subgroup of 35 patients with so-called t(11;14) translocations showed clear benefit from the addition of venetoclax, with a median PFS that was not reached compared with 9.5 months with placebo (HR 0.11, 95% CI 0.02-0.56, P=0.002). There were very few deaths in these patients — one and two in the investigational and placebo arms, respectively — with no observed difference for overall survival (HR 0.34, 95% CI 0.03-3.84, P=0.363).
Whether venetoclax will have a role in the treatment of multiple myeloma is unclear. In March of this year, the FDA placed a partial hold on trials involving the drug for multiple myeloma based on the overall survival data from BELLINI. Patients still on treatment and deriving benefit in ongoing studies were allowed to continue therapy following re-consent, and with anti-infective prophylaxis.
There is the Canova trial: A Study of Venetoclax and Dexamethasone Compared With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (CANOVA), ClinicalTrials.gov Identifier: NCT03539744