Diffuse Large B Cell Lymphoma

Venetoclax Plus R-CHOP as First-Line Treatment for Diffuse Large B-Cell Lymphoma

A Phase 2 study of Venetoclax plus R-CHOP as First-Line Treatment for Patients with Diffuse Large B-Cell Lymphoma


In an abstract published in the journal Blood on February 4, 2021, investigators from the CAVALLI clinical trial, reported on the phase 2 study of assessing the safety and efficacy of venetoclax added to R-CHOP for first-line diffuse large B-cell lymphoma.  The study included patients who had protein overexpression of BCL-2 by immunohistochemistry, 2+.  Patients are at least 18 years of age and had to have untreated diffuse large B-cell lymphoma.  An ECOG up to 2 was allowed.  

Venetoclax was administered at 800 mg daily on days 4 through 10 of cycle 1 and days 1 through 10 for cycles 2 through cycle 8, concurrently with 8 cycles of rituximab and 6-8 type cycles of CHOP on 21-day cycles.  The primary endpoints were safety, tolerability and complete response at the end of treatment.  Secondary endpoints were progression free survival as well as overall survival.  Comparative analysis was performed using cao-variate adjusted R-CHOP controls from the GOYA/B 021005 study which has been set as a benchmark for safety and efficacy.  

Safety and efficacy analysis included 206 patients.  The complete response at the end of therapy was 69% of the overall population.  In the BCL-2 immunohistochemistry positive subgroups, this trend was maintained.  After a medium follow-up of 32.2 months, trends were observed for improved investigator assessed progression free survival for the combination therapy in the overall population, with a hazard ratio 0.61, 95% confidence interval 0.43–0.87 and BCL-2 immunohistochemistry subgroup, hazard ratio 0.55, 95% confidence interval 0.34–0.89 versus R-CHOP. The incidence of grade 3 or 4 hematologic adverse events was reported as 86%. Treatment-related mortality was 2% which was not increased.  Dose intensity for chemotherapy with similar between the 2 groups.  

The authors concluded “the addition of venetoclax to R-CHOP in first-line diffuse large B-cell lymphoma demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high risk BCL-2 IHC positive patient subgroups“