A phase II study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.
Fiche publication
Date publication
septembre 2020
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre
Tous les auteurs :
Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illes A, Johnson NA, Larouche JF, Lugtenburg PJ, Patti C, Salles GA, Trneny M, de Vos S, Mir F, Samineni D, Kim SY, Jiang Y, Punnoose E, Sinha A, Clark E, Spielewoy N, Humphrey K, Bazeos A, Zelenetz AD
Lien Pubmed
Résumé
The phase II 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-positive). Eligible patients ≥18 years with previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2-5. Venetoclax 800 mg (days 4-10, cycle 1 and days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and CHOP (6-8 cycles); 21-day cycles. Primary endpoints: safety, tolerability, and complete response (CR) at end of treatment (EOT). Secondary endpoints: 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-positive subgroups. With 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-positive subgroups (HR = 0.55, 95% CI, 0.34-0.89), versus 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 versus 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-positive patient subgroups.
Référence
Blood. 2020 Sep 21;: