Polatuzumab Vedotin Combined With R-ICE (PolaR-ICE) as Second-Line Therapy in Diffuse Large B-Cell Lymphoma

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765.