The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.

1st Department of Medicine Charles University General Hospital Prague Czech Republic

AbbVie North Chicago IL

Azienda Ospedali Riuniti Villa Sofia Cervello Palermo Italy

CHU de Nancy Université de Lorraine Vandoeuvre lès Nancy France

CHU de Québec Hôpital de l'Enfant Jésus Quebec City QC Canada

Concord Hospital University of Sydney Sydney NSW Australia

David Geffen School of Medicine University of California Los Angeles CA

Department of Hematology Faculty of Medicine University of Debrecen Debrecen Hungary

F Hoffmann La Roche Ltd Basel Switzerland; and

Genentech Inc South San Francisco CA

Hospices Civils de Lyon Centre Hospitalier Lyon Sud University of Lyon Pierre Bénite France

HOVON Lunenburg Lymphoma Phase 1 2 Consortium Erasmus MC Cancer Institute Rotterdam The Netherlands

Jewish General Hospital Montreal QC Canada

Memorial Sloan Kettering Cancer Center New York NY

Paracelcus Medical University Salzburg Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials Salzburg Austria

Roche Products Limited Welwyn Garden City United Kingdom

Royal Marsden Hospital Sutton Surrey United Kingdom

Sarah Cannon Research Institute Tennessee Oncology Nashville TN

Université de Lille Centre Hospitalier Universitaire Lille France

Blood. 2021 Feb 4;137(5):577-579. doi: 10.1182/blood.2020008924. PubMed

Blood. 2021 Apr 1;137(13):1844. doi: 10.1182/blood.2021011330. PubMed

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ClinicalTrials.gov
NCT02055820