Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update

Author:

Dreyling Martin1ORCID,Fowler Nathan Hale23ORCID,Dickinson Michael4ORCID,Martinez-Lopez Joaquin5ORCID,Kolstad Arne6,Butler Jason7ORCID,Ghosh Monalisa8ORCID,Popplewell Leslie9ORCID,Chavez Julio C.10ORCID,Bachy Emmanuel11ORCID,Kato Koji12,Harigae Hideo13ORCID,Kersten Marie José14ORCID,Andreadis Charalambos15ORCID,Riedell Peter A.16ORCID,Ho P. Joy17ORCID,Pérez-Simón José Antonio18,Chen Andy I.19,Nastoupil Loretta J.20ORCID,von Tresckow Bastian2122ORCID,María Ferreri Andrés José23ORCID,Teshima Takanori24ORCID,Patten Piers E. M.2526ORCID,McGuirk Joseph P.27ORCID,Petzer Andreas L.28,Offner Fritz29,Viardot Andreas30,Zinzani Pier Luigi3132ORCID,Malladi Ram33,Paule Ines34,Zia Aiesha34ORCID,Awasthi Rakesh35,Han Xia36,Germano Davide34,O’Donovan Darragh37,Ramos Roberto36,Maier Harald J.34,Masood Aisha36,Thieblemont Catherine38ORCID,Schuster Stephen J.39ORCID

Affiliation:

1. 1Department of Medicine, Medical Clinic III, Ludwig-Maximilian-University Hospital, Munich, Germany

2. 2The University of Texas MD Anderson Cancer Center, Houston, TX

3. 3BostonGene, Waltham, MA

4. 4Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

5. 5Hospital 12 De Octubre, Complutense University, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

6. 6Oslo University Hospital, Oslo, Norway

7. 7Royal Brisbane Hospital, Herston, QLD, Australia

8. 8Division of Hematology/Oncology, Michigan Medicine University of Michigan, Ann Arbor, MI

9. 9City of Hope Comprehensive Cancer Center, Duarte, CA

10. 10Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL

11. 11Clinical Hematology, Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France

12. 12Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan

13. 13Department of Hematology, Tohoku University Hospital, Sendai, Japan

14. 14Department of Hematology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands, on behalf of Stichting Hemato-Oncologie voor Volwassenen Nederland/Lunenburg Lymphoma Phase I/II Consortium

15. 15Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA

16. 16David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL

17. 17Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia

18. 18Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, Seville, Spain

19. 19Oregon Health and Science University, Portland, OR

20. 20Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX

21. 21Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany

22. 22Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

23. 23Unit of Lymphoid Malignancies, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milan, Italy

24. 24Department of Hematology, Hokkaido University Hospital, Sapporo, Japan

25. 25Comprehensive Cancer Centre, King’s College London, London, United Kingdom

26. 26Department of Haematology, King’s College Hospital, London, United Kingdom

27. 27Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer l Center, Westwood, KS

28. 28Internal Medicine I, Ordensklinikum Linz Barmherzige Schwestern-Elisabethinen, Linz, Austria

29. 29Universitair Ziekenhuis Gent, Ghent, Belgium

30. 30Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

31. 31IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia “Seràgnoli,” Bologna, Italy

32. 32Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy

33. 33Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

34. 34Novartis Pharma AG, Basel, Switzerland

35. 35Novartis Institutes for BioMedical Research, East Hanover, NJ

36. 36Novartis Pharmaceuticals Corporation, East Hanover, NJ

37. 37Novartis Pharmaceuticals Corporation, Dublin, Ireland

38. 38Service d'hémato-oncologie, Hôpital Saint-Louis, Paris, France

39. 39Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

Abstract

Abstract Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor–positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.

Publisher

American Society of Hematology

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