Real-world outcomes of polatuzumab, rituximab, and lenalidomide in frail pts with diffuse large B-cell lymphoma.

e19055 Background: Patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are elderly, frail, or have cardiac comorbidities are frequently ineligible for anthracycline-based chemotherapy and are underrepresented in clinical trials. Chemotherapy-sparing regimens incorporating antibody–drug conjugates and immunomodulatory agents may provide an alternative treatment strategy. Therefore, polatuzumab vedotin (Pola), rituximab, and lenalidomide (Pola-R 2 ) was evaluated in a real-world cohort of pts with aggressive DLBCL. Methods: A retrospective analysis of consecutive pts with DLBCL treated with Pola-R 2 at a single institution was performed. Pola at 1.8mg/kg and rituximab at 375mg/m 2 were administered on day 1 of each 21-day cycle with planned lenalidomide 10 mg on days 1–14. Interim response assessment was obtained after cycle 4 and end of treatment assessment after cycle 8. Response was assessed using 2014 Lugano criteria and Clonoseq MRD. The primary objective was feasibility and tolerability; secondary objective was early disease control. Kaplan Meir analysis was used for survival outcomes. Results: Twenty pts with median age of 81 yo (range 50–92) and median ECOG performance status of 3 (range 2–4) were included. Comorbidity burden was substantial, with 75% of pts having significant cardiac disease, 30% with renal disease and 30% with chronic pulmonary disease. 40% (n=8) received Pola-R 2 in the frontline setting and 60% in second line or beyond; 9 with anthracycline exposure. 85% of pts had stage IV disease and 70% had non germinal center B-cell. At a median follow-up of 7.7 months (range 2–13), median overall survival (OS) was not reached and median progression-free survival (PFS) was 8.6 months (95% CI 5.4- undefined). Estimated 6-month PFS and OS were 69% and 73%, respectively. Interim PET assessment after four cycles demonstrated CR in 50%, and PR in 25%. Of the 11 pts who completed treatment at time of submission, 90.1% achieved CR, of whom 81.8% had undetectable MRD. Improvement in performance status following treatment permitted consolidative treatment with stem cell transplant in 4 of these pts (1 autologous, 3 allogeneic). Overall, treatment was well tolerated, with only 2 discontinuations for quality of life. Neutropenia occurred in 80% of pts within the first 4 cycles leading to reduction of Lenalidomide to 7 days in 75% of pts. Only 1 hospitalization occurred while on treatment. Conclusions: In this elderly and frail population with high-risk DLBCL, Pola-R 2 was feasible with encouraging early disease control, including PET-defined complete responses and MRD negativity. While follow-up is shorter, these findings compare favorably with historical outcomes reported for attenuated chemoimmunotherapy regimens such as R-mini-CHOP. This supports further prospective evaluation of chemotherapy-sparing strategies for anthracycline-ineligible pts with aggressive lymphoma.