Polatuzumab Vedotin Plus R-CHOP Improves Progression-Free Survival in Newly Diagnosed DLBCL

Take-aways

• Polatuzumab vedotin is a CD79b-targeting antibody-drug conjugate currently approved for the treatment of patients with relapsed/refractory DLBCL in combination with bendamustine and rituximab.
• Polatuzumab vedotin plus a modified R-CHOP regimen of rituximab, cyclophosphamide, doxorubicin, and prednisone reduced the relative risk of disease progression, relapse, or death by 27% compared with R-CHOP.
• The safety profile of pola-R-CHP was comparable to that of R-CHOP, including cytopenias and peripheral neuropathy.

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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. These findings, which were presented as a late-breaking abstract at the 2021 American Society of Hematology Annual Meeting, represent the first significant improvement over standard of care for newly diagnosed DLBCL in the past 2 decades, according to study authors.

R-CHOP is curative in only approximately 60% to 70% of patients with newly diagnosed DLBCL, the researchers noted. Although the trial found no significant difference in complete response (CR) rates or overall survival (OS) at 2 years, participants who received the new drug combination were less likely to need additional treatment compared with those receiving R-CHOP.

“I think this could be a practice-changing result,” said Gilles Salles, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York. “This is the first randomized phase III study that has shown a benefit in patients with first-line DLBCL. It shows that it is possible to significantly reduce disease progression, including in patients with difficult-to-treat subtypes.”

Polatuzumab vedotin is a CD79b-targeting antibody-drug conjugate currently approved by the US 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 6 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.

After a median follow-up of 28.2 months, PFS, the study’s primary endpoint, was higher in patients treated with pola-R-CHP compared with R-CHOP (hazard ratio [HR], 0.73; 95% CI 0.57-0.95; P < .02). The respective 2-year PFS rates for pola-R-CHP and R-CHOP were 76.7% and 70.2%.

The secondary endpoint of event-free survival (EFS) also favored pola-R-CHP (HR, 0.75; 95% CI 0.58-0.96; P = .02). While the PET-CT CR rate at the end of treatment was not significantly different between groups, disease-free survival results suggested responses to pola-R-CHP were more durable. Rates of OS at 2 years also were comparable between pola-R-CHP and R-CHOP (88.7% and 88.6%).

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.

Based on the similar OS rates, researchers noted that further follow-up could help elucidate whether pola-R-CHP brings a survival benefit in the longer term. However, Dr. Salles said the new regimen should reduce the risk of relapse and help patients avoid intensive treatments such as hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy.

Disclosures: This research was supported by Hoffmann-La Roche. Study authors report financial relationships with Hoffmann-La Roche, the manufacturer of polatuzumab vedotin.

Reference

Tilly H, Morschhauser F, Sehn LH, et al. The POLARIX study: polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy in patients with previously untreated diffuse large B-cell lymphoma. Abstract LBA-1. Presented at the 2021 American Society of Hematology Annual Meeting, December 14, 2021.