Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study

Grzegorz S Nowakowski, Dok Hyun Yoon, Anthea Peters, Patrizia Mondello, Erel Joffe, Isabelle Fleury, Richard Greil, Matthew Ku, Reinhard Marks, Kibum Kim, Pier Luigi Zinzani, Judith Trotman, Dan Huang, Eva E Waltl, Mark Winderlich, Nuwan C Kurukulasuriya, Sumeet Ambarkhane, Georg Hess, Gilles Salles, Grzegorz S Nowakowski, Dok Hyun Yoon, Anthea Peters, Patrizia Mondello, Erel Joffe, Isabelle Fleury, Richard Greil, Matthew Ku, Reinhard Marks, Kibum Kim, Pier Luigi Zinzani, Judith Trotman, Dan Huang, Eva E Waltl, Mark Winderlich, Nuwan C Kurukulasuriya, Sumeet Ambarkhane, Georg Hess, Gilles Salles

Abstract

Purpose: In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with patient-level matched observational cohorts treated with National Cancer Care Network (NCCN)/European Society for Medical Oncology (ESMO)-listed systemic therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Patients and methods: Data were collected from health records of eligible patients aged ≥18 years with histologically confirmed DLBCL who had received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients from L-MIND were matched with patients from the RE-MIND2 observational cohort using estimated propensity score-based 1:1 nearest-neighbor matching, balanced for nine covariates. The primary analysis compared tafasitamab plus lenalidomide with patients who received any systemic therapy for R/R DLBCL (pooled in one cohort) or bendamustine plus rituximab (BR) or rituximab plus gemcitabine and oxaliplatin (R-GemOx; as two distinct cohorts). The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and time-to-event outcomes.

Results: In RE-MIND2, 3,454 patients were enrolled from 200 sites in North America, Europe, and Asia-Pacific. Strictly matched pairs of patients consisted of tafasitamab plus lenalidomide versus systemic therapies pooled (n = 76 pairs), versus BR (n = 75 pairs), and versus R-GemOx (n = 74 pairs). Significantly prolonged OS was reported with tafasitamab plus lenalidomide versus systemic pooled therapies [hazard ratios (HR): 0.55; P = 0.0068], BR (HR: 0.42; P < 0.0001), and R-GemOx (HR: 0.47; P = 0.0003).

Conclusions: RE-MIND2, a retrospective observational study, met its primary endpoint, demonstrating prolonged OS with tafasitamab plus lenalidomide versus BR and R-GemOx. See related commentary by Cherng and Westin, p. 3908.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
RE-MIND2 study design. A, Assessment periods. Patients who received at least two therapy lines for DLBCL were assigned an index date (index date 2L, 3L, or 4L) for each eligible therapy line. Pre-index period, time between initial DLBCL diagnosis and index date of treatments (2L, 3L, or 4L). Index date, start of R/R DLBCL treatment (2L, 3L, or 4L). Observational period, time between index date and end of follow-up including survival assessment. Baseline, 28 days of baseline assessment prior to index date. B, Patient flow and disposition of enrolled patients into the MAS for tafasitamab plus lenalidomide versus systemic therapies pooled, BR, and R-GemOx. *, FAS included patients who met the eligibility/noneligibility criteria of RE-MIND2 and patients from the L-MIND study who received at least one dose of tafasitamab and one dose of LEN; all patients had a minimum of 6 months' follow-up. †, FAS_elig included a subset of patients from FAS who were eligible for matching. ‡, MAS_Pool included 1:1 matched patients from the L-MIND study and the observational cohort using baseline covariates. §, FAS_BR included patients who met the eligibility/noneligibility criteria of RE-MIND2 and received BR, and patients from the L-MIND study who received at least one dose of tafasitamab and one dose of LEN; all patients had a minimum of 6 months' follow-up. ¶, FAS_elig_BR included a subset of patients from FAS_BR who were eligible for matching. #, MAS_BR included 1:1 matched patients from the L-MIND study and those who received BR. **, FAS_R-GemOx included patients who met the eligibility/noneligibility criteria of RE-MIND2 and received R-GemOx, and patients from the L-MIND study who received at least one dose of tafasitamab and one dose of LEN; all patients had a minimum of 6 months' follow-up. ††, FAS_elig_R-GemOx included a subset of patients from FAS_R-GemOx who were eligible for matching. ‡‡, MAS_R-GemOx included 1:1 matched patients from the L-MIND study and those who received R-GemOx. BR, bendamustine + rituximab; DLBCL, diffuse large B-cell lymphoma; elig, eligible; ePS, estimated propensity score; FAS, full analysis set; L, therapy line; LEN, lenalidomide; MAS, matched analysis set; R-GemOx, rituximab + gemcitabine + oxaliplatin; R/R, relapsed/refractory.
Figure 2.
Figure 2.
Kaplan–Meier plot of overall survival in patients who received one (dotted lines) and one or more (solid lines) prior lines of therapy. A, Tafasitamab plus lenalidomide versus systemic therapies pooled. B, Tafasitamab plus lenalidomide versus BR. C, Tafasitamab plus lenalidomide versus R-GemOx. BR, bendamustine + rituximab; CI, confidence interval; HR, hazard ratio; KM; Kaplan–Meier; L, line; LEN; lenalidomide; NR, not reached; R-GemOx, rituximab + gemcitabine + oxaliplatin; Tafa, tafasitamab.
Figure 3.
Figure 3.
Kaplan–Meier plot of duration of response. A, Tafasitamab plus lenalidomide versus systemic therapies pooled. B, Tafasitamab plus lenalidomide versus BR. C, Tafasitamab plus lenalidomide versus R-GemOx. BR, bendamustine + rituximab; KM; Kaplan–Meier; LEN; lenalidomide; R-GemOx, rituximab + gemcitabine + oxaliplatin; Tafa, tafasitamab.
Figure 4.
Figure 4.
Kaplan–Meier plot of progression-free survival. A, Tafasitamab plus lenalidomide versus systemic therapies pooled. B, Tafasitamab plus lenalidomide versus BR. C, Tafasitamab plus lenalidomide versus R-GemOx. BR, bendamustine + rituximab; CI, confidence interval; HR, hazard ratio; KM; Kaplan–Meier; LEN; lenalidomide; R-GemOx, rituximab + gemcitabine + oxaliplatin; Tafa, tafasitamab.

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