Multinational phase 3 trial of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin for relapsed or refractory DLBCL

Patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unfavorable prognosis after failure of first-line treatment. The multinational phase 3 POLARGO trial evaluated efficacy and safety of the combination of polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) in patients with transplant-ineligible R/R DLBCL. Following a Pola-R-GemOx safety run-in (n=15), patients with R/R DBLCL ineligible for autologous stem cell transplant were 1:1 randomized to receive Pola-R-GemOx (n=129) or R-GemOx (n=126) every 21 days for up to eight cycles. The primary endpoint was overall survival (OS). The median follow-up was 24.6 months. Patients receiving Pola-R-GemOx versus R-GemOx had a significantly lower risk of death (HR 0.60; p=0.0017) and progression or death (HR 0.37; p<0.001) with a median OS or 19.5 months versus 12.5 months. The most common grade 3-4 adverse events were thrombocytopenia and neutropenia. Peripheral neuropathy was more common with Pola-R-GemOx (53%) than with R-GemOx (29%) and was primarily grade 1; fatal AEs ocurred in 12% versus 4%, largely driven by infections (including COVID-19). The authors conclude that addition of Pola to R-GemOx significantly improved OS among patients with transplant-ineligible R/R DLBCL.