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Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial

Research output: Contribution to journalArticlepeer-review

Nathan Hale Fowler, Michael Dickinson, Martin Dreyling, Joaquin Martinez-Lopez, Arne Kolstad, Jason Butler, Monalisa Ghosh, Leslie Popplewell, Julio C. Chavez, Emmanuel Bachy, Koji Kato, Hideo Harigae, Marie José Kersten, Charalambos Andreadis, Peter A. Riedell, P. Joy Ho, José Antonio Pérez-Simón, Andy I. Chen, Loretta J. Nastoupil, Bastian von Tresckow & 15 more Andrés José María Ferreri, Takanori Teshima, Piers E.M. Patten, Joseph P. McGuirk, Andreas L. Petzer, Fritz Offner, Andreas Viardot, Pier Luigi Zinzani, Ram Malladi, Aiesha Zia, Rakesh Awasthi, Aisha Masood, Oezlem Anak, Stephen J. Schuster, Catherine Thieblemont

Original languageEnglish
JournalNature Medicine
Early online date17 Dec 2021
DOIs
Accepted/In press10 Nov 2021
E-pub ahead of print17 Dec 2021

Bibliographical note

Funding Information: The study was sponsored and designed by Novartis Pharmaceuticals Corporation and was approved by the IRB at each participating institution. Data were analyzed and interpreted by the sponsor and the authors. All authors reviewed the manuscript and approved of the final version before submission. We vouch for the data and analysis and for the adherence of the study to the protocol. We thank A. A. Abozeid (former employee of Novartis) for his contributions to the analyses presented herein. Medical writing support was provided by R. Parthasarathy (Healthcare Consultancy Group) and was funded by Novartis Pharmaceuticals Corporation. Funding Information: N.H.F. is an advisor or consultant for Roche/Genentech, TG Therapeutics, Verastem, Bayer, Celgene and Novartis and reports research support from Roche, Celgene, Gilead Sciences, TG Therapeutics, Novartis, AbbVie and BeiGene. M. Dickinson is an advisor or consultant for Novartis, Bristol-Myers Squibb, Gilead Sciences, Roche and Janssen; has received honoraria from Roche, Amgen, MSD, Janssen, Bristol-Myers Squibb and Novartis; has participated in speaker bureau for Novartis; and reports research support from Novartis, Roche, Takeda, Celgene and MSD. M. Dreyling is an advisor or consultant for AstraZeneca, Bayer/Vital, BeiGene, Celgene/Jazz, Genmab, Gilead Sciences, Incyte, Janssen-Cilag, Novartis and Roche; has participated in speaker bureau for Amgen, AstraZeneca, Bayer Health, Celgene, Gilead Sciences, Janssen-Cilag and Roche Pharma AG; and reports research support from AbbVie, Bayer, Celgene, Janssen-Cilag and Roche Pharma AG and travel support from Celgene, Janssen-Cilag and Roche Pharma AG. J.M.L. is an advisor or consultant for Janssen, Novartis, BMS, Incyte, Astellas and GlaxoSmithKline; reports research support from Bristol-Myers Squibb and Roche; has participated in speaker bureau for Janssen, Novartis, BMS, Incyte, Astellas and GlaxoSmithKline; and owns stock in Altum Sequencing. A.K. is an advisor or consultant for Nordic Nanovector and reports research support from Merck and Nordic Nanovector and travel support from Nordic Nanovector. J.B. is an advisor or consultant for Novartis and has participated in speaker bureau for Novartis. M.G. declares no competing interests. L.P. reports honoraria from Pfizer and Roche and travel support from Novartis. J.C.C. is a consultant for Kite/Gilead, Novartis, Karyopharm Therapeutics, MorphoSys, TeneBio, AbbVie, ADC Therapeutics and Janssen; has participated in speaker bureau for AstraZeneca, BMS, BeiGene and MorphoSys; and reports research support from Merck, AstraZeneca and ADC Therapeutics (Inst.). E.B. is an advisor or consultant for Roche and Incyte and reports research support from Takeda and Amgen, financial support from Roche, Janssen, Celgene, Novartis and Gilead and nonfinancial support from Roche, BeiGene, Celgene and AbbVie. K.K. is an advisor or consultant for AbbVie, AstraZeneca, Celgene, Chugai, Eisai, Janssen and Novartis; has received honoraria from Celgene, Chugai, Janssen, Kyowa Kirin, Merck, Mundi, Novartis, Ono, Sumitomo Dainippon and Takeda; and reports research support from AbbVie, Celgene, Chugai, Eisai, Janssen, Kyowa Kirin, Ono, Novartis and Takeda. H.H. has received honoraria from BMS, Novartis, Chugai and Janssen and reports research support from Astellas. M.J.K. is an advisor or consultant for, and has received honoraria and travel support from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Kite/Gilead, Merck, Miltenyi Biotec, Novartis and Roche; and reports research support from Celgene, Roche and Takeda. C.A. is an advisor or consultant for Gilead Sciences, Kite Pharma, Karyopharm Therapeutics, Atara Biotherapeutics, Incyte, TG Therapeutics and Epizyme; reports research support from Novartis, GlaxoSmithKline, Amgen, Juno Therapeutics, Celgene and Merck; and reports travel support from Gilead Sciences and Kite Pharma. P.A.R. reports grants and personal fees from Kite/Gilead and Celgene/BMS; grants from MorphoSys, Xencor and Calibr; personal fees from Takeda, Verastem, Karyopharm Therapeutics, BeiGene and Bayer; and grants, personal fees and nonfinancial support from Novartis. P.J.H. reports travel support from Celgene, Janssen, La Jolla and Novartis. J.A.P.S. is an advisor or consultant for Novartis, Janssen, Roche, Jazz Pharmaceuticals, Amgen and Gilead Sciences; reports research support from Novartis, Janssen, Pfizer, Roche and Takeda; reports travel support from Roche, Gilead Sciences and Janssen; and reports patents, royalties or other intellectual property from Entourage Bioscience on cannabinoid derivatives. A.I.C. is an advisor or consultant for MorphoSys, Mesoblast and Genentech and has received clinical trial support (Inst.) from Novartis for submitted work. L.J.N. has received honoraria from Bayer, Celgene, Gilead and Novartis and reports research support from Celgene and Genentech. B.v.T. is an advisor or consultant for BMS/Celgene, Novartis, Pentixafarm, Amgen, Pfizer, Takeda, Merck Sharp & Dohme and Gilead Kite; has received honoraria from Novartis, Roche Pharma AG, Takeda and Merck Sharp & Dohme; reports research funding from Novartis (Inst), Merck Sharp & Dohme (Inst) and Takeda (Inst); and reports travel support from AbbVie, AstraZeneca, Kite-Gilead, Merck Sharp & Dohme, Takeda and Novartis. A.J.M.F. declares no competing interests. T.T. is an advisor or consultant for Merck, Novartis and Takeda; has received honoraria from Bristol-Myers Squibb, Fuji Pharma, Kyowa Kirin, Merck, Nippon Shinyaku, Pfizer, Takeda and Teijin Pharma; reports research support from Astellas, Chugai Pharma, Kyowa Kirin, Novartis and Sanofi; reports grants from the Japan Society for the Promotion of Science and Japan Science and Technology Agency; and has received assistance with manuscript preparation for Janssen and Novartis. P.E.M.P. has received grants or contracts from Roche and Gilead; has received honoraria from AbbVie, Gilead, Janssen and Novartis; has received travel support from AbbVie and Janssen; and has participated on a data safety monitoring board or advisory board for AbbVie and Novartis. J.P.M. is an advisor or consultant for Juno; has received honoraria from AlloVir, Juno and Kite; reports research support from AlloVir, Astellas, Bellicum, Fresenius Biotech, Gamida Cell, Juno, Kite, Novartis and Pluristem; has participated in speaker bureau for Kite; and has received assistance with manuscript preparation for ArticulateScience LLC. A.L.P. is an advisor or consultant for, and reports honoraria from, Novartis, BMS, Pfizer, Roche, Takeda, Celgene-BMS and Incyte and travel support from Celgene-BMS and Pfizer. F.O. declares no competing interests. A.V. is advisor or consultant for Novartis, Kite/Gilead, BMS, Amgen and Roche and reports personal fees and nonfinancial support from Roche, BMS, Novartis, Amgen, Takeda, AstraZeneca and Kite/Gilead. P.L.Z. is an advisor or consultant for Merck Sharp & Dohme, Bristol-Myers Squibb, Celgene, Gilead, Infinity, Janssen, Pfizer, Roche and Takeda. R.M. is an advisor or consultant for Roche and reports travel support from Amgen, Novartis and Gilead Sciences. A.Z., R.A., A.M. and O.A. are employees of Novartis. S.J.S. is an advisor or consultant for Acerta, AlloGene, AstraZeneca, BeiGene, Celgene/Juno, Genentech/Roche, LoxoOncology, Novartis and Tessa Therapeutics; has received honoraria from Acerta, AlloGene, AstraZeneca, BeiGene, Celgene, Genentech/Roche, LoxoOncology, Novartis, Nordic Nanovector, Pfizer and Tessa Therapeutics; has participated in a steering committee for AbbVie, Celgene, Novartis, Juno, Nordic Nanovector and Pfizer; reports research support from AbbVie, Acerta, Celgene/Juno, DTRM Bio, Genentech, Incyte, Merck, Novartis, Portola and TG Therapeutics; and holds a patent with Novartis. C.T. has received honoraria from Celgene, AbbVie, Bayer, Janssen, Roche, Incyte, Novartis and Gilead and reports research funding from Roche and travel support from Roche, Janssen-Cilag, Kite/Gilead and Novartis. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

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King's Authors

Abstract

Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8–20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8–78.3) and ORR 86.2% (95% confidence interval, 77.5–92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.

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