Importance of Early Rescue and Relative Dose-Intensity in the Salvage Therapy with Tafasitamab-Lenalidomide in Diffuse Large B-Cell Lymphoma: Real-Life Study in Spain (GELTAMO)

Introduction Therapy of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains challenging, particularly for ineligible patients for intensive therapy. Tafasitamab-lenalidomide (T/L) represents an effective treatment option based on the L-MIND, phase 2 trial findings. However, various real-world studies (RWS) have reported mixed outcomes. This study aims to describe the real-world outcomes of R/R DLBCL treated with T/L in Spain, focusing on prognostic factors influencing overall response rate (ORR), complete remission (CR), progression-free survival (PFS) and overall survival (OS), to determine the optimal practice setting for this therapy. Methods This retrospective multicenter RWS was conducted by the Spanish Group of Lymphoma (GELTAMO). Patients included were treated with T/L in an expanded access program opened in Spain from June 2021 to September 2022, and as per clinical practice from October 2022 to December 2023. To avoid selection bias, all patients who received at least one partial dose of Tafasitamab were included as in the intention to treat population (safety population). Efficacy was evaluated only in patients who had received at least one full cycle of the combined T/L therapy (efficacy population). Results Ninety-nine patients who received at least one dose of Tafasitamab were included, with 83 receiving at least one full cycle of T/L. The median age at T/L was 78 years (47-93), with 90% being older than 60 years; 32% had an ECOG PS>1; the median CIRS score was 6 (0-21); the median number of previous lines of therapy was 2 (1-13), with 45% relapsing after a previous CR and 55% progressing or refractory to the previous line. 76% of the patients in the safety cohort and 73% of the efficacy cohort would have not been eligible for the L-MIND trial. In the efficacy cohort, the median follow-up was 16 months (95%CI: 8-24). The ORR was 61%, with a CR of 42%. The median PFS was 10.9 months and median OS was 26.4 months, with 12m-PFS and OS rates of 44% and 60%, and 18m-PFS and OS of 43% and 56% respectively. PFS was significantly better in patients with ECOG PS 0-1 (HR 0.47; p=0.013), in those who received T/L in first or second relapse (HR 0.53; p=0.044) and non-refractory patients to the previous line (HR 0.48; p=0.024). Disease characteristics before T/L, age, CIRS or response after the first line, did not influence outcome. Patients obtaining a CR showed excellent outcomes with 18m-PFS and OS of 73% and 80%, respectively. Treatment was generally well-tolerated. The most common grade 3-4 adverse events were neutropenia (42%), infection (27%) and anemia (20%). A relative dose-intensity (RDI) of lenalidomide lower than 85% was associated with significantly worse PFS and OS. Fifty-three (53%) patients died during the follow-up period. The primary causes of death were disease progression in 41 cases (77%). Eleven patients died due to toxicity or unrelated causes: 8 from infections (including 3 severe COVID19 pneumonia), two from secondary malignancies, one from progressive multifocal leukoencephalopathy and one for unknown causes. Conclusions In this real-world Spanish cohort treated with T/L, the treatment was well tolerated regardles age or comorbidities. The optimal setting for T/L appears to be in the first and second relapse, in patients who were not refractory to the previous line and with good ECOG PS (0-1). Age or CIRS have limited impact. RDI was associated with better PFS and OS. Patients achieving CR exhibited particularly favorable outcomes.