For the substantial portion of patients with diffuse large B-cell lymphoma (DLBCL) with overexpression of the BCL2 protein, combining the BCL2 inhibitor venetoclax with standard chemotherapy may improve response rates, according to results from the phase II CAVALLI trial. However, patients who received venetoclax experienced a higher rate of adverse events (AEs) compared with a historical control group who received chemotherapy alone.
In the CAVALLI trial, investigators, led by Franck Morschhauser MD, PhD, of Centre Hospitalier Régional Universitaire in Lille, France, studied the safety and efficacy of venetoclax plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), then compared these outcomes with controls in the phase III GOYA trial who received R-CHOP alone. (GOYA compared anti-CD20 monoclonal antibody obinutuzumab versus rituximab in addition to CHOP chemotherapy in patients with previously untreated DLBCL).
The present study included 208 adults with DLBCL, an International Prognostic Index score of 2 to 5, an Eastern Cooperative Oncology Group performance status of ≤2, and at least one measurable lesion ≥1.5 cm. Patients were assigned to receive six cycles of R-CHOP plus venetoclax (800 mg on days 4-10 of cycle 1, and days 1-10 of cycles 2-8). Per study protocol, two additional cycles of venetoclax plus rituximab were permitted per physician choice.
CAVALLI participants were matched with 564 patients from the GOYA trial. Patient characteristics were well matched, Dr. Morschhauser noted, except for a larger number of patients with higher-stage disease and BCL2 immunohistochemistry (IHC)- positive disease in the CAVALLI group.
The complete response (CR) rates (primary endpoint) did not differ significantly between the two cohorts: 69.2 percent versus 62.8 percent, respectively (95% CI 0-17.6). However, venetoclax appeared to improve CR rates among patients with BCL2-positive disease and double-hit lymphoma (TABLE).