A chemotherapy-free regimen of sintilimab, rituximab, and lenalidomide ± polatuzumab vedotin in elderly patients with newly diagnosed diffuse large B-cell lymphoma

Abstract Our previous pilot study demonstrated that the combination of sintilimab, rituximab, and lenalidomide (sR2) is effective and well tolerated in older patients with diffuse large B-cell lymphoma (DLBCL). Therefore, we continued to expand the sample size to explore the efficacy and safety of sR2 ± polatuzumab vedotin in older patients with de novo DLBCL. Eligible patients were ≥70 years old, or ≥60 years with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, newly diagnosed DLBCL. Patients received up to eight 28-day cycles of lenalidomide (10 mg orally, days 1–21), rituximab (375 mg/m² IV, day 1), sintilimab (200 mg IV, day 1), and optionally polatuzumab vedotin (1.8 mg/kg IV, day 1; for 6 cycles). Response assessments were conducted after cycles 4 and 8. Patients achieving partial or complete response (CR) after induction received maintenance lenalidomide (10 mg/day, days 1–21 of each 28-day cycle) for up to 2 years or until disease progression or unacceptable toxicity. The primary endpoint was CR rate at the end of induction; secondary endpoints included 2-year progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and treatment-emergent adverse events (TEAEs). Until May 7, 2025, 27 patients were enrolled. The median age was 77 years (range, 68–91), and 2 patients (7.4%) had ECOG PS ≥2. At the end of induction, 80.8% (21/26) achieved a response, with 85.7% (18/21) achieving CR. Among the 6 patients treated with sR2 plus polatuzumab vedotin, 5 achieved CR. After a median follow-up of 13.4 months, the estimated 2-year PFS and OS were 60.8% and 82.7%, respectively. The most common grade 3–4 hematologic toxicities were neutropenia (22.2%), thrombocytopenia (14.8%), and anemia (11.1%). No treatment-related deaths were observed. The chemotherapy-free regimen of sR2± polatuzumab vedotin demonstrates promising efficacy and a favorable safety profile in older patients with DLBCL. These findings warrant further prospective validation.