According to the results of the phase III POLARGO trial reported by Matasar et al in the Journal of Clinical Oncology, adding polatuzumab vedotin-piiq to rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) significantly improved overall survival compared with standard rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with transplant-ineligible relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The study was designed to address the need for more effective treatment options for patients whose disease has progressed after first-line therapy but who are not candidates for autologous stem cell transplant or chimeric antigen receptor T-cell therapy.
Study Details
The international, open-label trial enrolled patients between February 2020 and May 2023 at 64 centers across 16 countries. After a 15-patient safety run-in, 255 patients with relapsed or refractory DLBCL who were ineligible for transplant were randomly assigned to receive either Pola-R-GemOx (n = 129) or R-GemOx alone (n = 126) every 21 days for up to eight cycles. The primary endpoint was overall survival in the intention-to-treat population.
The median patient age was 65 years (range = 20–89 years). A total of 168 patients (65.9%) had disease refractory to their most recent treatment, 165 (64.7%) had received only one prior line of therapy, and 195 (76.5%) had advanced-stage disease at enrollment.
Key Results
After a median follow-up of 24.6 months, the risk of death was significantly reduced among patients receiving Pola-R-GemOx vs those receiving R-GemOx alone (hazard ratio = 0.60, 95% confidence interval [CI] = 0.43–0.83, P = .0017). Median overall survival improved from 12.5 months (95% CI = 8.9 months–15.8 months) with R-GemOx to 19.5 months (95% CI = 13.3 months to not estimable) with the polatuzumab vedotin–containing regimen. Overall survival rates were 64.5% and 50.2% at 12 months and 44.0% and 33.2% at 24 months, respectively.
Grade 3 or 4 adverse events occurred in 73 patients in each cohort, with the most common being thrombocytopenia and neutropenia. Fatal adverse events were more common in the investigational arm (11.7% vs 4.0%), largely because of infections, including COVID-19 during the pandemic period in which the study was conducted. The investigators noted, however, that treatment-related grade 5 adverse events occurred at similar rates between the treatment groups (3.1% vs 2.4%).
The investigators concluded: “Pola-R-GemOx significantly improved [overall survival] compared with R-GemOx, offering an additional treatment option in patients with transplant-ineligible [relapsed or refractory] DLBCL.”
Matthew Matasar, MD, of Rutgers Cancer Institute, New Brunswick, New Jersey, is the corresponding author for Journal of Clinical Oncology article.
DISCLOSURE: The study was funded by Genentech, Inc./F. Hoffmann–La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.
