The combination of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) reduced the relative risk of disease progression, relapse, or death by 27% in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the current standard of care, R-CHOP. This is according to research presented as a late-breaking abstract at the 2021 American Society of Hematology Annual Meeting by Hervé Tilly, MD, of Centre Henri Becquerel and University of Rouen in France.
Polatuzumab vedotin is a CD79b-targeting antibody-drug conjugate currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory DLBCL in combination with bendamustine and rituximab.
The phase III POLARIX study compared pola-R-CHP with R-CHOP in 879 patients with previously untreated DLBCL (median age = 65 years; range = 19-80). Most patients (62%) had an International Prognostic Index of 3-5.
Patients were randomized to receive either six cycles of pola-R-CHP with a vincristine placebo (n=440) or R-CHOP with a polatuzumab vedotin placebo (n = 439).
On day 1, patients received polatuzumab vedotin 1.8 mg/kg or vincristine 1.4 mg/m2, intravenous (IV) rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and placebo. Oral prednisone 100 mg was administered once daily on days 1 through 5.
The primary endpoint of the study was investigator-assessed progression-free survival (PFS). Investigator-assessed event-free survival (EFS), independent review committee–assessed complete response (CR) rate at the end of treatment by PET-CT, disease-free survival (DFS), overall survival (OS), and safety were additional endpoints.
After a median follow-up of 28.2 months, PFS was higher in patients treated with pola-R-CHP compared with R-CHOP (hazard ratio [HR] = 0.73). The respective two-year PFS rates for pola-R-CHP and R-CHOP were 76.7% and 70.2%.
EFS was also superior in the pola-R-CHP group compared with R-CHOP. While the PET-CT CR rate at the end of treatment was not significantly different between groups, DFS results suggested responses to pola-R-CHP were more durable. No difference in OS was observed between the two cohorts.
The safety profile of pola-R-CHP was comparable to that of R-CHOP. The rate of grade 3-4 adverse events (AEs) in each group was 57.7% and 57.5%, respectively. The rates of serious AEs (34% vs. 30.6%), grade 5 AEs (3% vs. 2.3%), and AEs leading to dose reduction (9.2% vs. 13%) were also similar.