-Author name in bold denotes the presenting author
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608 Long-Term Clinical Outcomes and Correlative Efficacy Analyses in Patients (Pts) with Relapsed/Refractory Follicular Lymphoma (r/r FL) Treated with Tisagenlecleucel in the Elara TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological IV
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022: 4:45 PM

Martin Dreyling, MD1, Michael Dickinson, MD2, Joaquin Martinez Lopez3*, Arne Kolstad, MD, PhD4*, Jason P Butler, MBBS, MMedSc5, Monalisa Ghosh, MD6, Leslie L. Popplewell, MD, FACP, MPH7, Julio Chavez8, Emmanuel Bachy, MD, PhD9*, Koji Kato, MD, PhD10*, Hideo Harigae, MD, PhD11, Marie Jose Kersten, MD, PhD12,13, Charalambos Andreadis, MD, MSCE14*, Peter A. Riedell, MD15*, Phoebe Joy Ho, MBBS(Syd) DPhil(Oxon) FRACP FRCPA FFSc(RCPA)16*, Jose A. Perez-Simon, MD, PhD17, Andy Chen, MD, PhD18, Loretta J. Nastoupil, MD19, Bastian von Tresckow, MD20, Andrés J M Ferreri, MD21, Takanori Teshima, M.D., Ph.D.22, Piers E.M. Patten23,24*, Joseph P. McGuirk, DO25, Andreas Petzer, MD26, Fritz Offner, MD, PhD27, Andreas Viardot, MD28, Pier Luigi Zinzani, MD, PhD29,30, Ram Malladi, MD31*, Ines Paule32*, Aiesha Zia32*, Rakesh Awasthi, PhD33*, Xia Han, MS34*, Davide Germano32*, Darragh O'Donovan, PhD35*, Roberto Ramos, MD34*, Aisha Masood, MD34, Catherine Thieblemont, MD, PhD36, Nathan H. Fowler, MD37 and Stephen J. Schuster, MD38*

1Medizinische Klinik III, LMU Klinikum, Munich, Germany
2Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of Melbourne, Melbourne, Australia
3Hospital 12 De Octubre, Complutense University, CNIO, Madrid, Spain
4Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway
5Department of Haematology and BMT, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
6Michigan Medicine University of Michigan, Ann Arbor, MI
7Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
8Moffitt Cancer Center, University of South Florida, Tampa, FL
9Department of Hematology, Hospices Civils de Lyon, Lyon Sud University Hospital, Pierre Benite, France
10Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan
11Tohoku University Hospital, Sendai, Japan
12On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Amsterdam, Netherlands, Amsterdam, Netherlands
13University of Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
14Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
15The University of Chicago Comprehensive Cancer Center, Chicago, IL
16Royal Prince Alfred Hospital and University of Sydney, Camperdown, Sydney, NSW, Australia
17Instituto de Biomedicina de Sevilla (IBiS), UGC-Hematología, Hospital Universitario Virgen del Rocío/ CSIC/ CIBERONC, Universidad de Sevilla, Sevilla, Spain
18Oregon Health and Science University, Portland, OR
19The University of Texas MD Anderson Cancer Center, Houston, TX
20Department I of Internal Medicine, West German Cancer Center Essen, Essen, Germany
21Lymphoma Unit, Dept of Onco-hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy
22Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
23Comprehensive Cancer Centre, King’s College London, London, United Kingdom
24Department of Haematology, King’s College Hospital, London, United Kingdom
25Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS
26Internal Medicine I, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria
27UZ Gent, Gent, Belgium
28Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany
29Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
30IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seragnoli”Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy
31Cambridge University Hospitals NHS Foundation Trust, Cambridge, CA, United Kingdom
32Novartis Pharma AG, Basel, Switzerland
33Novartis Institutes for BioMedical Research, East Hanover, NJ
34Novartis Pharmaceuticals Corporation, East Hanover, NJ
35Novartis Pharmaceuticals Corporation, Dublin, Ireland
36Hôpital Saint-Louis, Paris, France
37The University of Texas, MD Anderson Cancer Center, Houston, TX
38Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

Background: Tisagenlecleucel is the first CAR-T cell therapy approved in the United States and European Union for r/r FL in the third-line or later setting. In the primary analysis of the single-arm, open-label, Phase II ELARA trial, tisagenlecleucel demonstrated high response rates and an excellent safety profile in adult pts with high-risk r/r FL. Herein, we report >2-year follow-up data on the continued durability of response (DOR), longer-term safety, as well as biomarker and pharmacokinetic analyses from the ELARA trial.

Methods: Eligible pts had r/r FL (grades 1-3A) following ≥2 lines of therapy that included an anti-CD20 antibody and an alkylating agent or had relapsed after autologous stem cell transplant (SCT). Bridging chemotherapy was permitted. Following lymphodepleting (LD) chemotherapy, pts received single-dose tisagenlecleucel (0.6-6×108 CAR+ viable T cells). Baseline clinical factors, tumor microenvironment (TME) assessment, blood soluble factors, and circulating blood cells were correlated with clinical response and progression-free survival (PFS). Cellular kinetics were determined by measurement of transgene levels by quantitative polymerase chain reaction.

Results: Among 94 pts evaluable for efficacy [median follow-up of 28.9 months (mo)], complete response rate was 68% (95% CI, 57.7-77.3) and overall response rate was 86.2% (95% CI, 77.5-92.4). Median PFS was not reached (NR); the estimated 24 mo-PFS post infusion was 57.4% (95% CI, 46.2, 67.0; Figure). The estimated 24 mo-DOR and OS post infusion were 64.6% (77.8% for pts with CR) and 87.7% (95% CI, 78.3, 93.2), respectively. No new safety signals were reported. Neurological events (NEs) were reported in 12 (12.3%) pts including 1 pt with probable progressive multifocal leukoencephalopathy who had prior grade 4 immune effector cell-associated neurotoxicity syndrome. Three new deaths (total 13 deaths) occurred during this longer-term follow-up period [progressive disease (PD), n=1; serious adverse events (SAEs), n=2, urothelial bladder carcinoma and post allogeneic SCT (alloSCT) complications]. No new deaths were treatment related. A total of 23 (24%) pts received at least one subsequent therapy post infusion. Of these, 4 pts received alloSCT, and one pt received only localized radiotherapy. Persistence of the CAR transgene was observed for up to 925 days (median, 210 days; range, 13 to 925 days). Eight pts had SARS-COV-2 infection at the time of data cut-off.

Among all parameters tested, elevated tumor burden [TB; total metabolic tumor volume (TMTV) ≥240 cm3] at baseline (pre-LD chemotherapy), progression of disease within 2 years of initial chemoimmunotherapy (POD24), and >4 nodal areas at inclusion were clinical factors that correlated significantly with lower efficacy. Furthermore, baseline serum IL-10 and TNF-α levels were highly correlated with TB (Spearman correlation = 0.80 and 0.86, respectively (both P<0.001), with higher levels significantly associated with non-response/relapse and shorter PFS. Additionally, baseline TME was characterized by fluorescence immunohistochemistry, and an increase in LAG3+ exhausted T cells (≥3% of total T cells) was the only factor that significantly associated with shorter PFS (median PFS, 5.9 mo vs NR, P=0.0017). Also, decreased CD8+ cytotoxic T cells and increased CD19+ B cells in peripheral blood at baseline were associated with poor outcome. POD24, >4 nodal areas at inclusion, baseline TB, and tumor infiltrated LAG3+CD3+ cells remained significant in multivariate Cox models for PFS analysis.

Cellular kinetics shows that the mean in vivo maximal expansion (Cmax) in pts with no POD24 was higher compared with pts with POD24. Pts with high TB, based on TMTV at baseline, had a shorter DOR relative to pts with low TB.

Conclusions: Updated long-term data from the ELARA trial demonstrated robust durable responses >2 years post infusion, with a continued favorable safety profile. Correlative analyses suggest that high-risk disease characteristics (elevated TB at baseline, POD24, >4 nodal areas at inclusion), exhausted T cells in the TME, and increased IL-10 and TNF-α levels are associated with worse long-term outcomes following tisagenlecleucel in pts with r/r FL.

Disclosures: Dreyling: Lilly/Loxo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead/Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Abbvie: Research Funding; Beigene: Consultancy. Dickinson: Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD, Amgen: Honoraria; Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD: Consultancy; Roche, Novartis, Kite, Gilead, MSD, Takeda, Celgene: Research Funding. Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Chavez: Epyzime: Honoraria; ADC Therapeutics: Research Funding; Janssen: Research Funding; Merck: Research Funding; Astrazeneca: Research Funding; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; AdiCet: Consultancy; GenMab: Consultancy. Bachy: Kite, Gilead, Novartis, Roche, Incyte, Miltenyi Biotech, Takeda, Sanofi: Honoraria; Roche, Gilead, ADC Therapeutics, Takeda, Novartis, Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen, BMS: Research Funding; Hospices Civils de Lyon: Current Employment. Kato: Novartis: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Other: Grants or contracts from any entity ; Chugai: Consultancy, Honoraria, Other: Grants or contracts from any entity ; Meiji: Consultancy, Honoraria; Kyowa-Kirin: Honoraria, Other: Grants or contracts from any entity ; Takeda: Honoraria, Other: Grants or contracts from any entity ; AbbVie: Other: Grants or contracts from any entity ; Eisai: Other: Grants or contracts from any entity ; Janssen: Other: Grants or contracts from any entity ; Celgene: Other: Grants or contracts from any entity ; Ono: Other: Grants or contracts from any entity . Harigae: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Symbio: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Novartis: Honoraria. Kersten: Kite, a Gilead Company: Honoraria, Research Funding; BMS/Celgene: Honoraria, Research Funding; Adicet Bio: Honoraria; Takeda: Honoraria; Roche: Honoraria, Research Funding; Novartis: Honoraria; Miltenyi Biotech: Honoraria. Andreadis: Merck & Co., Inc.: Research Funding; Novartis: Research Funding; BMS: Honoraria; Kite: Honoraria. Riedell: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sana Biotechnology: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Calibr: Research Funding; Tessa Therapeutics: Research Funding; Fate Therapeutics: Research Funding; Xencor: Research Funding. Ho: Regeneron: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Antengene: Membership on an entity's Board of Directors or advisory committees. Perez-Simon: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, and Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, and Expenses; GILEAD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, and Expenses; JAZZ: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, and Expenses; ALEXION: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, and Expenses; ABBVIE: Research Funding; PFIZER: Research Funding. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Nastoupil: Genentech/Roche, MEI, Takeda: Other: DSMC; ADC Therapeutics, BMS, Caribou Biosciences, Epizyme, Genentech/Roche, Gilead/Kite, Genmab, Janssen, MEI, Morphosys, Novartis, Takeda: Honoraria; BMS, Caribou Biosciences, Epizyme, Genentech, Gilead/Kite, Genmab, Janssen, IGM Biosciences, Novartis, Takeda: Research Funding. von Tresckow: Pentixafarm: Consultancy; Novartis: Consultancy, Honoraria, Other: NA, Research Funding; IQVIA: Consultancy; MSD: Consultancy, Honoraria, Other: NA, Research Funding; Roche: Consultancy, Honoraria, Other: NA; Takeda: Consultancy, Honoraria, Other: NA, Research Funding; Pfizer: Consultancy; AstraZeneca: Honoraria, Other: NA; Amgen: Consultancy; Allogene: Consultancy; Abbvie: Other: NA; Miltenyi: Consultancy; BMS: Honoraria, Other: NA; Cerus: Consultancy; Gilead/Kite: Consultancy, Honoraria, Other: NA, Research Funding; Incyte: Consultancy, Honoraria. Ferreri: Amgen: Research Funding; Genmab: Research Funding; ADC Therapeutics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; PletixaPharm: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Adienne: Speakers Bureau; Pfizer: Research Funding; Ospedale San Raffaele srl: Patents & Royalties: NGR-hTNAF/RCHOP in relapsed/refractory PCNSL; SNGR-hTNF in brain tumours; Hutchison Medipharma: Research Funding; BMS: Research Funding; Pharmacyclics: Research Funding; Beigene: Research Funding. Teshima: Luca Science Inc.: Research Funding; Asahi Kasei Pharma: Research Funding; Eisai: Research Funding; Astellas: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Manuscript preparation; Fuji Pharma: Research Funding; NIPPON SHINYAKU: Research Funding; Janssen: Other: Manuscript preparation; Sanofi: Research Funding; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Research Funding; ONO: Research Funding; SHIONOGI: Research Funding; Priothera SAS: Research Funding; Otsuka: Research Funding; AbbVie: Honoraria; Celgene: Honoraria; Meiji Seika Pharma: Other: non-financial support; DAIICHI SANKYO: Other: non-financial support ; AstraZeneca: Other: non-financial support ; Roche Diagnostics: Other: non-financial support . Patten: ROCHE: Research Funding; GILEAD SCIENCES: Honoraria, Research Funding; ABBVIE: Honoraria; ASTRA ZENECA: Honoraria; JANSSEN: Honoraria; NOVARTIS: Honoraria; Beigene: Honoraria. McGuirk: Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Orca Bio: Research Funding; Nextar: Consultancy, Honoraria; Sana: Honoraria; CRISPR Therapeutics: Consultancy; In8bio, Inc.: Other: IIT Clinical Trial. Petzer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau. Viardot: Kite Gilead: Consultancy, Honoraria, Other: Support for meeting attendance; Novartis: Consultancy, Honoraria, Other: Support for meeting attendance; BMS: Consultancy, Honoraria, Other: Support for meeting attendance; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Other: Support for meeting attendance; Janssen-Cilag: Honoraria, Other: Support for meeting attendance; Astra Zeneca: Honoraria, Other: Support for meeting attendance; Incyte: Consultancy, Other: Support for meeting attendance. Zinzani: Beigene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; University of Bologna: Current Employment. Paule: Novartis: Current Employment. Awasthi: Novartis: Current Employment, Current equity holder in private company. Han: Novartis: Current Employment. Germano: Novartis: Current Employment. O'Donovan: Novartis: Current Employment. Ramos: Novartis: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Thieblemont: Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda: Consultancy, Honoraria, Other: Travel Support; Incyte: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support; Novartis: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel Support; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel Support. Fowler: Roche: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BostonGene Corporation: Current Employment, Other: Leadership. Schuster: AstraZeneca: Consultancy; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Research Funding; Genmab: Consultancy; Fate Therapeutics: Consultancy; Roche: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding; Legend Biotech: Consultancy; Loxo Oncology: Consultancy; MorphoSys: Consultancy; Mustang Biotech: Consultancy; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties: related to CD19 CAR T cells , Research Funding; Regeneron: Consultancy; AbbVie: Research Funding; Adaptive Biotechnologies: Research Funding; DTRM: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding.

*signifies non-member of ASH