TOPLINE

Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) reduced the risk for death by 40% compared with rituximab, gemcitabine, and oxaliplatin (R-GemOx) alone in patients with transplant-ineligible relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The combination more than doubles complete response rates from 19.0% to 40.3% and extends median overall survival from 12.5 months to 19.5 months.

METHODOLOGY

• Real-world data show that many eligible patients do not receive CAR T-cell therapy, with only 25% in the second-line and 36% in the third-line receiving this treatment in the US, highlighting the need for effective alternative treatment options. In the relapsed or refractory setting, polatuzumab vedotin with bendamustine and rituximab showed an improved end-of-treatment complete response rate and overall survival benefit, but exploring additional chemotherapy partners may be beneficial to improve treatment options and maximize clinical benefit.
• Researchers conducted a multicenter, open-label, phase 3 trial (POLARGO) at 64 sites in 16 countries, following a safety run-in phase (n = 15) and a randomized controlled trial phase.
• A total of 255 patients with relapsed or refractory DLBCL not otherwise specified or transformed indolent lymphoma, who were ineligible for autologous stem cell transplant, were randomly assigned 1:1 to receive Pola-R-GemOx (n = 129) or R-GemOx (n = 126).
• Patients received polatuzumab vedotin (1.8 mg/kg) plus rituximab (375 mg/m²), gemcitabine (1000 mg/m²), and oxaliplatin (100 mg/m²) intravenously, or R-GemOx alone intravenously, every 21 days for up to eight cycles.
• The primary endpoint was overall survival (OS) in the intention-to-treat population, with key secondary endpoints including investigator-assessed progression-free survival (PFS), and independent review committee-assessed complete response rate and overall response rate at end of treatment.
• The median follow-up duration was 24.6 months for OS, and survival outcomes were estimated using the Kaplan-Meier method with comparisons between groups using a two-sided log-rank test.

TAKEAWAY

• Pola-R-GemOx demonstrated a statistically significant 40% reduction in the risk for death compared with R-GemOx (hazard ratio [HR], 0.60; P = .0017), with a median OS of 19.5 vs 12.5 months.
• Investigator-assessed PFS showed a 63% reduction in the risk for progression or death with Pola-R-GemOx compared with R-GemOx (HR, 0.37; P < .0001), with a median PFS of 7.4 vs 2.7 months.
• Independent review committee-assessed complete response rate at end of treatment was more than doubled with Pola-R-GemOx at 40.3% vs 19.0% with R-GemOx (P < .0001).
• Survival benefits with Pola-R-GemOx were consistent across most prespecified subgroups, including patients with primary refractory disease, those receiving second-line treatment, and both activated B-cell-like and germinal center B-cell-like cell-of-origin subtypes.

IN PRACTICE

“Pola-R-GemOx significantly improved OS compared with R-GemOx, offering an additional treatment option in patients with transplant-ineligible R/R [relapsed or refractory] DLBCL,” the authors of the study wrote.

SOURCE

This study was led by Matthew Matasar, MD, Rutgers Cancer Institute in New Brunswick, New Jersey, and Zhiming Li, MD, Sun Yat-sen University Cancer Center in Guangzhou, China. It was published online on July 6 in the Journal of Clinical Oncology. 

LIMITATIONS

A notable limitation was that the study was designed before CAR T-cell therapy was approved in the second-line setting for relapsed or refractory DLBCL and before polatuzumab vedotin was incorporated into first-line therapy, and there are currently no robust data to support the use of polatuzumab vedotin in the relapsed or refractory DLBCL setting in patients who received first-line polatuzumab vedotin-containing therapies. Another limitation is the use of R-GemOx as a control arm, which the authors acknowledge is increasingly an outdated standard of care for this patient population. The higher rate of fatal adverse events was largely due to an increased incidence of infections, including COVID, as the study coincided with the pandemic’s onset, which may have influenced the survival outcomes.

DISCLOSURES

This study was supported by Genentech, Inc/F. Hoffmann-La Roche Ltd. Matasar disclosed receiving honoraria from Genentech, Roche, Bayer, Pharmacyclics, Seagen, Takeda, and other companies; consulting or advisory roles with Genentech, Roche, Bayer, and others; and research funding from Genentech, Roche, and other organizations. Li disclosed having no relevant financial relationships. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.