ABCL-088 Subgroup Analysis in RE-MIND2: An Observational, Retrospective Cohort Study of Tafasitamab + Lenalidomide Versus Systemic Therapies in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Abstract

Tafasitamab+lenalidomide (LEN), a chemo-free immunotherapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), demonstrated efficacy in autologous stem cell transplant-ineligible patients in the single-arm L-MIND study (NCT02399085). RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared patient outcomes from L-MIND with matched patient cohorts treated with other systemic therapies. Prolonged overall survival (OS) with tafasitamab+LEN was detected compared to a cohort of pooled systemic therapies (PST), bendamustine+rituximab (BR), rituximab+gemcitabine+oxaliplatin, polatuzumab vedotin+BR (pola-BR), and rituximab+LEN (R2). Comparable OS was detected versus CD19 chimeric antigen receptor T-cell therapies (CAR-T). However, limited information is available on the comparative effectiveness of tafasitamab+LEN in specific subpopulations. This study aimed to determine the relative effectiveness of tafasitamab+LEN versus other treatments for R/R DLBCL in clinically relevant patient subgroups in the absence of head-to-head trials. The L-MIND cohort was matched with RE-MIND2 patients using estimated propensity score-based 1:1 nearest neighbor matching balanced for a minimum of six covariates. Sensitivity analyses were conducted. The study was conducted at academic, public, and private hospitals in Europe, North America, and the Asia-Pacific region. Patients were ≥18 years old with histologically confirmed DLBCL and ≥2 prior systemic therapies for DLBCL, including ≥1 anti-CD20 therapy. Data are presented for tafasitamab+LEN versus PST, versus pola-BR, versus R2, and versus CAR-T. Hypothesis-generating analyses were conducted for patient subgroups of number of extranodal sites (ENS) (0-1 vs. ≥2) and elevated lactate dehydrogenase (LDH) (yes vs. no). The primary endpoint was OS. Of 3,454 patients enrolled, 961, 106, 106, and 149 were treated with PST, pola-BR, R2, and CAR-T, resulting in 76, 24, 33, and 37 matched pairs for patients receiving tafasitamab+LEN, respectively. Hazard ratios for OS for patients with ≥2 ENS were 0.803, 0.524, 0.478, and 1.459, and for patients with elevated LDH were 0.627, 0.585, 0.420, and 1.663, for comparisons of tafasitamab+LEN versus PST, pola-BR, R2, and CAR-T, respectively. There was a trend towards favoring tafasitamab+LEN in most patient subgroups. The combination may be associated with improved OS versus selected systemic therapies for certain patients with high-risk disease. These analyses are not powered for statistical comparison and should be interpreted with caution. Funding: MorphoSys AG.