RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma

Abstract

RE-MIND2 (NCT04697160) compared patient outcomes from the L-MIND (NCT02399085) trial of tafasitamab+lenalidomide with those of patients treated with other therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are autologous stem cell transplant ineligible. We present outcomes data for three pre-specified treatments not assessed in the primary analysis. Data were retrospectively collected from sites in North America, Europe, and the Asia Pacific region. Patients were aged ≥18 years with histologically confirmed DLBCL and received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients enrolled in the observational and L-MIND cohorts were matched using propensity score-based 1:1 nearest-neighbor matching, balanced for six covariates. Tafasitamab+lenalidomide was compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR), rituximab+lenalidomide (R2), and CD19-chimeric antigen receptor T-cell (CAR-T) therapies. The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and progression-free survival. From 200 sites, 3,454 patients were enrolled in the observational cohort. Strictly matched patient pairs consisted of tafasitamab+lenalidomide versus pola-BR (n = 24 pairs), versus R2 (n = 33 pairs), and versus CAR-T therapies (n = 37 pairs). A significant OS benefit was observed with tafasitamab+lenalidomide versus pola-BR (HR: 0.441; p = 0.034) and R2 (HR: 0.435; p = 0.012). Comparable OS was observed in tafasitamab+lenalidomide and CAR-T cohorts (HR: 0.953, p = 0.892). Tafasitamab+lenalidomide appeared to improve survival outcomes versus pola-BR and R2, and comparable outcomes were observed versus CAR-T. Although based on limited patient numbers, these data may help to contextualize emerging therapies for R/R DLBCL. CLINICAL TRIAL REGISTRATION: NCT04697160 (January 6, 2021).

Keywords: DLBCL; Lenalidomide; Real-world; Relapsed/Refractory; Tafasitamab.

Fig. 1

Flow of enrolled patients into matched analysis sets for the tafasitamab plus lenalidomide, pola-BR, R2, and CAR-T therapies. Abbreviations: CAR-T, CD19 chimeric antigen receptor T-cell therapy; ePS, estimated propensity score; FAS, full analysis set of RE-MIND2-eligible patients with a minimum of 6 months’ follow-up; LEN, lenalidomide; pola-BR, polatuzumab vedotin + bendamustine + rituximab; R2, rituximab + lenalidomide. *Included patients who met the eligibility/non-eligibility criteria of RE-MIND2 and who received at least one dose of tafasitamab and one dose of LEN; all patients had a minimum of 6 months’ follow-up. ^†Included patients who met the eligibility/non-eligibility criteria of RE-MIND2 and received pola-BR; all patients had a minimum of 6 months’ follow-up. ^‡Included patients who met the eligible/non-eligible criteria of RE-MIND2 and received R2; all patients had a minimum of 6 months’ follow-up. ^§Included patients who met the eligibility/non-eligibility criteria of RE-MIND2 and received CAR-T; all patients had a minimum of 6 months’ follow-up. ^¶Included a subset of enrolled patients who received pola-BR and were eligible for matching. ^#Included a subset of enrolled patients who received R2 and were eligible for matching. **Included a subset of enrolled patients who received CAR-T and were eligible for matching. ^††Included patients who received pola-BR and were matched 1:1 with patients from L-MIND based on ePS. ^‡‡Included patients who received R2 and were matched 1:1 with patients from L-MIND based on ePS. ^§§Included patients who received CAR-T and were matched 1:1 with patients from L-MIND based on ePS

Fig. 2

Kaplan–Meier plot of overall survival. (A) Tafasitamab plus lenalidomide versus pola-BR. (B) Tafasitamab plus lenalidomide versus R2. (C) Tafasitamab plus lenalidomide versus CAR-T. Abbreviations: CAR-T, CD19 chimeric antigen receptor T-cell therapy; CI, confidence interval; HR, hazard ratio; KM, Kaplan–Meier; LEN, lenalidomide; OS, overall survival; pola-BR, polatuzumab vedotin + bendamustine + rituximab; R2, rituximab + lenalidomide; Tafa, tafasitamab

Fig. 3.

ORR and CR rate for tafasitamab plus lenalidomide versus pola-BR, R2, and CAR-T therapies. Abbreviations: CAR-T, CD19 chimeric antigen receptor T-cell therapy; CI, confidence interval; CR, complete response; LEN, lenalidomide; ORR, overall response rate; pola-BR, polatuzumab vedotin + bendamustine + rituximab; R2, rituximab + lenalidomide