Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

By H. Tilly, F. Morschhauser, L. Sehn, J. Friedberg, M. Trněný, J. Sharman, C. Herbaux, J. Burke, M. Matasar, S. Rai and 22 more. New England Journal of Medicine, 2021

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BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody–drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. We replaced vincristine with polatuzumab vedotin and compared the new regimen with R-CHOP. METHODS In this double-blind, placebo-controlled, international phase 3 study, patients aged 18–80 years with previously untreated intermediate- and high-risk DLBCL were randomized 1:1 to receive six cycles of pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary endpoint was investigator-assessed progression-free survival. Secondary endpoints included overall survival and safety. RESULTS Overall, 879 patients were enrolled (pola-R-CHP: n = 440; R-CHOP: n = 439). After a median follow-up of 28.2 months, the 2-year progression-free survival rate was 76.7% (95% CI, 72.7 to 80.8) versus 70.2% (95% CI, 65.8 to 74.6); progression-free survival was superior with pola-R-CHP versus R-CHOP (HR, 0.73 by Cox analysis; 95% CI, 0.57 to 0.95; P < 0.02). No difference was seen in overall survival between treatment arms; 2-year overall survival rate was 88.7% (95% CI, 85.7 to 91.6) in the pola-R-CHP arm, and 88.6% (95% CI, 85.7 to 91.6) in the R-CHOP arm (HR, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was comparable for pola-R-CHP versus R-CHOP. CONCLUSIONS In patients with previously untreated intermediate- and high-risk DLBCL, pola-R-CHP reduces the risk of disease progression, relapse, or death by 27% compared with R-CHOP, with a similar safety profile. CLINICAL TRIAL INFORMATION This study is registered at ClinicalTrials.Gov as: NCT03274492.

Subfields: Dermatology, Oncology, Pathology and Forensic Medicine

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