Work

Five‐year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the Phase II L‐MIND study

Year: 2023

Type: article

Abstract: Introduction: Tafasitamab, an anti-CD19 immunotherapy that enhances antibody-dependent cellular cytotoxicity and phagocytosis, received accelerated approval in the USA and conditional authorization in Europe in combination with lenalidomide (LEN) for patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) based on the results of the open-label, multicenter, single-arm, Phase II L-MIND study (NCT02399085; Salles G., et al. Lancet Oncol 2020, Duell J., et al. Haematologica 2021). Here, we report the final, 5-year follow-up of L-MIND. Data cut-off was 14 November 2022. Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, 1–3 prior systemic therapies (including a CD20-targeting regimen), and ECOG PS 0–2. Tafasitamab (12 mg/kg) was given for up to 12 cycles in combination with LEN (25 mg), then as monotherapy until disease progression (PD) or unacceptable toxicity. The primary endpoint was best objective response rate (ORR; complete response [CR] or partial response [PR], by independent radiology committee). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs). Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). Results: Of 81 pts enrolled, 80 were treated (full analysis set [FAS]). The ORR (FAS) of 56.2% [95% CI: 44.7–67.3], with CR of 40.0% [29.2–51.6] (n = 32) and PR of 16.2% [8.9–26.2] (n = 13), was generally consistent with the primary and 3-year analyses. Median DoR was not reached (NR) with median follow up (mFU) of 43.7 months [29.9–58.4]. Median PFS was 11.6 months [5.7–45.7] (mFU 36.7 [22.9–59.2]) and median OS was 33.5 months [18.3–NR] (mFU 65.6 [59.9–70.3]). At data cut-off, OS was >60 months in 21 pts (18 with best response of CR, 1 PR, 1 stable disease and 1 PD), including 14 with 1 pLoT and 7 with ≥2 pLoT. Pts with 1 pLoT (n = 40) in the FAS had higher ORR (65%; 50% CR [n = 20] and 15% PR [n = 6]) compared to pts with ≥2 pLoT (n = 40; 47.5%; 30% CR [n = 12] and 17.5% PR [n = 7]). However, median DoR was not reached for both subgroups, indicating similar long-term efficacy for responders. AEs were consistent with previous reports and manageable; incidence declined after transition from combination to tafasitamab monotherapy and again with monotherapy >2 years. Conclusions: The final, 5-year analysis of L-MIND showed prolonged durable responses with tafasitamab + LEN combination therapy, followed by long-term tafasitamab monotherapy, in pts with R/R DLBCL ineligible for ASCT, with median DoR not reached after 43.7 months mFU. No new safety signals were identified, confirming the tolerability profile observed with earlier data cuts. These long-term data suggest that this immunotherapy may have curative potential that is being explored in further studies. Encore Abstract - previously submitted to AACR 2023 The research was funded by: MorphoSys AG Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. J. Duell Research funding: MorphoSys AG, Regeneron P. Abrisqueta Consultant or advisory role: Janssen, Celgene, AbbVie, AstraZeneca Honoraria: Janssen, Celgene, AbbVie, AstraZeneca, Gilead Other remuneration: Speakers' bureau: Janssen, Celgene, AbbVie, AstraZeneca, Gilead M. Andre Research funding: Roche, Johnson & Johnson, Takeda Educational grants: Roche, Bristol-Myers-Squib, Celgene, Gilead, AbbVie, AstraZeneca Other remuneration: Advisory board: Takeda, Bristol-Myers-Squibb, Karyopharm, Gilead, Incyte. M. Augustin Consultant or advisory role: Bristol-Myers Squibb, MSD, Pfizer, PharmaMar, IPSEN, AstraZeneca, Novartis, Bayer, Roche Research funding: Bristol-Myers Squibb, MSD, MorphoSys AG, AstraZeneca, Pfizer, PharmaMar, IPSEN, Exelixis Educational grants: Lilly, Novartis, Bristol-Myers Squibb, PharmaMar, IPSEN, u, Merck G. Gaidano Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Incyte, Janssen, Roche Other remuneration: Speaker's Bureau: AbbVie, Janssen E. G. Barca Consultant or advisory role: Janssen, AbbVie, Gilead, Kiowa, EUSAPharma, Incyte, Lilly, BeiGene Educational grants: Janssen, AbbVie, EUSAPharma Other remuneration: Speakers' bureau: Janssen, AbbVie,Takeda, Kiowa, Roche, EUSAPharma, Incyte, BeiGene W. Jurczak Consultant or advisory role: MEI Pharma, Debiopharm, Loxo, Takeda, AstraZeneca, BeiGene Research funding: GSK, Acerta, BeiGene, Nordic Nanovector, Debiopharm, Incyte, Genentech, Janssen, Loxo, MEI Pharma, MorphoSys AG, Takeda, TG Therapeutics N. Kalakonda Consultant or advisory role: BMS/Celgene, Gilead/Kite, Hospira, Incyte, Janssen, Karyopharm, Roche, Takeda Research funding: Celgene, Gilead, Roche Other remuneration: Speakers' bureau: BMS/Celgene, Gilead/Kite, Hospira, Incyte, Janssen, Karyopharm, Roche, Takeda A. M. Liberati Consultant or advisory role: Incyte Honoraria: Bristol-Myers Squibb, Servier, Celgene, AbbVie, Amgen Research funding: Novartis, Janssen, AbbVie, Roche, Amgen, Sanofi Genzyme, Celgene, Bristol-Myers Squibb, Servier, Incyte, Pfizer, IQVIA, Doxopharma, Verastem, BeiGene, Oncopeptides, Karyopharm, Archigen, CTI BioPharma, Debiopharm, MorphoSys AG, FibroGen, MEI Pharma, Regeneron, Dr Reddy's Laboratories Spa K. J. Maddocks Honoraria: Pharmacyclics, MorphoSys AG, Bristol-Myers Squibb, Karyopharm Therapeutics, Kite Pharma/Gilead Company, ADC Therapeutics, AbbVie, AstraZeneca, BeiGene, Genmab, Genentech, Janssen, Lilly, Incyte Research funding: Pharmacyclics, Merck, Bristol-Myers Squibb T. Menne Honoraria: Kite/Gilead, Amgen, Novartis, Pfizer, Celgene/BMS, Daiichi Sankyo, Atara, Roche, Janssen Research funding: Janssen, AstraZeneca, Novartis Educational grants: Amgen, Jazz, Pfizer, Bayer, Kyowa Kirin, Celgene/BMS, Kite/Gilead, Janssen, Takeda Other remuneration: Honoraria for lectures: Kite/Gilead, Takeda, Janssen, Roche, Servier, Novartis, Celgene/BMS, Pfizer Z. Nagy Consultant or advisory role: Takeda, Janssen, AbbVie, Roche, Amgen, Servier, Astellas O. Tournilhac Consultant or advisory role: Takeda, AstraZeneca, BeiGene, Incyte, Janssen, Gilead, AbbVie, Roche, Sandoz, Blueprint A. Bakuli Employment or leadership position: MorphoSys AG Other remuneration: Statistical consultancy: Ludwig-Maximilians-University Hospital, Munich, Germany A. Amin Employment or leadership position: MorphoSys AG Stock ownership: Paion AG K. Gurbanov Employment or leadership position: MorphoSys AG G. Salles Consultant or advisory role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys AG, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, VelosBio, Bristol-Myers Squibb, BeiGene, Incyte, Miltenyi Biotec, Ipsen Honoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSys AG

Source: Hematological Oncology

DOI: 10.1002/hon.3164_323