Sintilimab, Rituximab and Lenalidomide (sR2) As First-Line Treatment in Elderly Patients with Diffuse Large B-Cell Lymphoma: A Single-Arm, Open-Label, Phase 2 Trial

The chemo-free combination of rituximab and lenalidomide (R2) has been showed activity in a significant proportion of older patients with diffuse large B-cell lymphoma (DLBCL). Lenalidomide could enhance the cytotoxicity induced by checkpoint blockade in vitro. Herein, we did a phase 2 trial of sintilimab, rituximab, and lenalidomide (sR2) to evaluate the efficacy and safety in older patients with de novo DLBCL. Eligible patients were aged older than70 years or older than 60 years with ECOG PS ≥ 2, newly diagnosed DLBCL. Patients were administered a maximum of 8 28-day cycles of 10 mg oral lenalidomide from days 1 to 21, IV rituximab 375 mg/m2 and sintilimab 200mg on day 1, with response assessment after cycles 4 and 8. Patients with partial response or complete response (CR) at cycle 8 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 2 years or until progression or unacceptable toxicity. The primary endpoint in this study was complete response rate (CRR) after 8 cycles or at the end of the induction treatment. The secondary end point was 2-year overall survival, progression-free survival, overall response rate (ORR) and treatment-emergent adverse events. Until April 9, 2024, A total of 18 older DLBCL patients were enrolled and 14 of them was evaluated. The median age of the patients in this study was 75 years old (range 68-70) and 2 (11.1%) patients had a poor performance status with an ECOG score of 2 or greater. 12 (85.7%) patients achieved an overall response at the end of the induction treatment, with 11 (78.6%) achieving a complete response. With a median follow up of 8.9 months, the 1-year progression-free survival and overall survival were 80.8% and 92.9%, respectively. Common grade 3-4 adverse events were hematological toxicities (neutropenia in 4 patients (28.6%), thrombocytopenia in 3 patients (21.4%), anemia in 3 (21.4%). No treatment-related deaths were reported. A chemotherapy-free sR2 regimen is clinically effective and safe and warrants further investigation in older patients with DLBCL.