Preliminary Result of Lenalidomide Combined with R-CHOP(R2-CHOP) in Newly Diagnosed Double-Expressor Diffuse Large B-Cell Lymphoma: A Prospective Phase II Clinical Trial

Background: Double expressor lymphoma (DEL) is a subtype of diffuse large B-cell lymphoma (DLBCL) defined as having increased expression of MYC (≥40%) and BCL-2 (≥50%) by immunohistochemistry (IHC). Patients with DEL have inferior outcomes when treated with standard immunochemotherapy. Previous studies illustrated that lenalidomide showed a significant clinical response in non-GCB DLBCL, and well tolerated when combined with R-CHOP. This study aims to investigate the efficacy and safety of lenalidomide combined with R-CHOP (R2-CHOP) in newly diagnosed DEL patients.

Methods: Histologic diagnosis of DLBCL and MYC/BCL-2 expression by IHC were confirmed by central pathology prior to study therapy. Treatment regimen included lenalidomide 25 mg/d orally days 1-10 per 21days, plus standard R-CHOP21 for 6 cycles. The primary end point was 2-year progression free survival (PFS) per independent central radiology review. Secondary end points included 2-year event-free survival (EFS), overall response rate (ORR), overall survival (OS), and safety.

Results: Between Oct 2019 and Aug 2021, 67 eligible patients were enrolled in this study. Median age was 58 (range 27-75) years. Forty-one (61.2%) patients were stage III-IV, and 35.8% of patients were IPI score ≥3. Non-GCB subtype was determined in 44 (65.7%) patients. Three patients detected double-hit lymphoma withdrew from the study per investigator's decision. Sixty patients were evaluable for response. Fifty-seven patients responded to therapy, with overall response rate of 95% (57/60), and complete response rate of 80% (48/60). With a median follow-up of 17.8 months, the estimated 1-year PFS rate was 85.3% (95%CI 75.9%-95.2%). And the 1-year EFS rate was 79% (95%CI 68.8%-90.3%). Median OS was not reached, and 1-year OS rate was 90.9% (95%CI 84.1%-98.1%). Grade 3 or 4 hematologic toxicities included neutropenia (67.2%), thrombocytopenia (19.4%), and anemia (4.5%). The most common nonhematologic adverse events were grade 1 to 2, including nausea, vomiting, fatigue, diarrhea, and mucositis. Grade 3 pneumonia occurred in 5 patients. Dose modification of lenalidomide or R-CHOP due to AEs were noted in 43.3% and 20.9% patients. No treatment-related death occurred in the study.

Conclusion: Our preliminary data indicate promising activity of lenalidomide combined with R-CHOP for newly diagnosed DEL patients. R2CHOP regimen was feasible, with predictable and manageable adverse events.

No relevant conflicts of interest to declare.

Lenalidomide is approved in treating multiple myeloma. However, previous studies illustrated that it showed a significant clinical response in non-GCB DLBCL, and well tolerated when combined with R-CHOP. Double expressor lymphoma (DEL) has aggressive behavior and lacks standard treatment. This study aims to investigate the efficacy and safety of lenalidomide combined with R-CHOP (R2-CHOP) in newly diagnosed DEL patients.