Adding Venclexta (venetoclax) to Velcade (bortezomib) and dexamethasone has shown promising effectiveness and an acceptable safety profile in multiple myeloma patients who progressed during or after at least one prior therapy, data from a Phase 1b clinical trial show.
Among patients who received a median of three prior therapies, 67% responded to the triple combination, including 42% who had very good partial responses. Those who responded lived for a median of 9.5 months without disease progression, the study found.
The results of the trial (NCT01794507) were reported in the article, “Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/ refractory MM,” published in the journal Blood.
The trial was designed to test the safety and effectiveness of the therapy combination in 66 patients with relapsed or refractory myeloma whose ages ranged from 39 to 79. Some of the patients — 26, or 39% — did not respond previously to Velcade.
Venclexta, a B-cell lymphoma 2 (BCL-2) inhibitor, is taken orally. Velcade is a myeloid cell leukemia sequence 1 (MCL-1) inhibitor. Both proteins act to unblock the cell death pathway in tumor cells, allowing them to die off naturally as they should in normal circumstances, although the way each protein does this varies.
The overall response rate to the treatment was 67% (44 of 66 patients). It was even higher (97%) in participants who were not refractory to Velcade and who had received one to three cancer therapies before the trial.
The combination of Venclexta, Velcade, and dexamethasone appeared generally well-tolerated.
Common adverse events included diarrhea (46%), constipation (41%), and nausea (38%). Roughly half of the participants experienced severe to life-threatening adverse events.
Due to disease progression, 46 patients (70%) discontinued the study.
One viral infection and four instances of disease progression were responsible for five deaths that occurred during the study.
“Overall, the clinical results seen with this combination are encouraging and support an ongoing phase 3 trial of this regimen,” Philippe Moreau, MD, head of the hematology department at University Hospital of Nantes in France, and colleagues wrote. “Agents that target these BCL-2 family members, including venetoclax and bortezomib, provide a novel therapeutic approach for multiple myeloma based on a strong mechanistic rationale.”
“These response rates were observed despite most patients (39 of 66) receiving a dose of venetoclax that was inferior to 800 mg per day,” the researchers wrote.