Efficacy and safety of pola-ICE, with or without rituximab in relapsed/refractory diffuse large B-cell lymphoma: A real-world multicenter study

Abstract Background: Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains a significant therapeutic challenge, with a continued need for more effective salvage regimens. Polatuzumab vedotin (Pola), an antibody-drug conjugate targeting CD79b, has demonstrated safety and efficacy when combined with bendamustine and rituximab in transplant-ineligible patients (pts) with relapsed DLBCL pts. We evaluated the safety and efficacy of Pola-ICE regimen—comprising polatuzumab vedotin, ifosfamide, carboplatin, and etoposide—with or without the addition of rituximab in R/R DLBCL pts in the real world. Methods: This multicenter retrospective study included 51 consecutive R/R DLBCL patients from three Chinese hospitals between January 2023 and June 2025. All patients received Pola-ICE: Pola 1.8 mg/kg (day 1), ifosfamide 4000 mg/m² (administered in two divided doses, days 1–2, with MESNA infusion), carboplatin AUC 4 (day 2), etoposide 100 mg/m² (days 1–3), repeated every 21 days up to 6 cycles. Rituximab (375 mg/m², day 1) was added at physician discretion. The primary endpoints were overall response rate (ORR) and complete response rate (CRR), assessed according to the 2014 Lugano classification. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: The cohort included 51 pts (median age 52 years, range 18–77) who received a median of two cycles of Pola-ICE (range 1–6), including 35.1% (23/51) with ≥2 prior lines of therapy (median 1, range 1–6). Baseline characteristics are shown in Table 1. Among the 51 pts，45 were evaluable for efficacy, 3 pts are still on treatment and pending initial assessment, and 3 patients were lost to follow-up. Of 45 pts, the best ORR was 75.5% (34/45) with 42.2% CR rate (19/45), 2 had stable disease and 9 had progressive disease. With a median follow-up of 15.1 months, the median PFS was 9.6 months (95% CI: 5.8–NA). OS data remained immature due to the limited follow-up period. 14 pts achieving CR demonstrated significantly longer PFS (11.5 months vs. 4.2 months, P=0.04) and OS (not reached vs. 10.1 months, P=0.01) compared with non-CR patients. . To date, 14 pts proceeded to CAR-T therapy, and 4 pts underwent ASCT consolidation. 48 pts have toxicity data available. The most common Grade 3-4 hematologic toxicities were neutropenia (33.3%, 16/48), thrombocytopenia (31.3%, 15/48), anemia (33.3%, 16/48) and febrile neutropenia (10.4%, 5/48) despite G-CSF prophylaxis. Grade 1-2 Peripheral neuropathy occurred in 14 (29.2%) pts and no Grade 5 adverse events were observed. Conclusion: Pola-ICE, with or without rituximab, demonstrated promising efficacy with high-quality responses and manageable toxicity in heavily pretreated R/R DLBCL pts. This salvage regimen may serve as a viable option for high-risk patients, potentially enabling subsequent curative-intent therapies.