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131 Efficacy of Tisagenlecleucel in Adult Patients (Pts) with High-Risk Relapsed/Refractory Follicular Lymphoma (r/r FL): Subgroup Analysis of the Phase II Elara Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Evolution of Immunotherapeutic Regimens in B-cell Lymphomas
Hematology Disease Topics & Pathways:
Biological, Clinical Trials, Adults, Lymphomas, B Cell Lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Clinically Relevant, Diseases, Therapies, Lymphoid Malignancies, Study Population
Saturday, December 11, 2021: 1:00 PM

Catherine Thieblemont, MD, PhD1, Michael Dickinson, MBBS2, Joaquin Martinez-Lopez, MD, PhD3*, Arne Kolstad, MD, PhD4*, Jason P Butler, MBBS, MMedSc5, Monalisa Ghosh, MD6, Leslie L. Popplewell, MD, FACP7, Julio C. Chavez, MD, MS8*, Emmanuel Bachy, MD, PhD9*, Koji Kato, MD, PhD10, Hideo Harigae, MD, PhD11, Marie Jose Kersten, MD, PhD12, Charalambos Andreadis, MD, MSCE13*, Peter A. Riedell, MD14, P. Joy Ho, MBBS15*, Jose Pérez-Simón, MD16, Andy Chen, MD, PhD17, Loretta Nastoupil, MD18, Bastian Von Tresckow, MD19*, Andres JM Ferreri, MD20, Takanori Teshima, M.D., Ph.D.21, Piers EM Patten, MB, ChB, FRCP, FRCPath, PhD22, Joseph P. McGuirk, DO23, Andreas Petzer, MD24*, Fritz Offner, MD, PhD25, Andreas Viardot, MD26, Pier Luigi Zinzani, MD, PhD27, Ram Malladi, MD28*, Aiesha Zia29*, C Lobetti Bodoni, MD, PhD29*, Aisha Masood, MD30, Stephen J. Schuster, MD31, Nathan H. Fowler, MD18 and Martin H. Dreyling, MD, PhD32

1Department of Hemato-Oncology, Saint Louis Hospital, Paris, France
2Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia
3Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Hospital Universitario 12 de Octubre, Complutense University, CNIO, Madrid, Spain
4Oslo University Hospital Radiumhospitalet, Oslo, NOR
5Royal Brisbane and Women's Hospital, Brisbane, Australia
6Michigan Medicine University of Michigan, Ann Arbor, MI
7Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
8Moffitt Cancer Center, Tampa, FL
9Hospices Civils de Lyon and Université Claude Bernard, Pierre-Bénite, France
10Kyushu University Hospital, Fukuoka, Japan
11Tohoku University Hospital, Sendai, Japan
12Amsterdam UMC, Dept. of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
13Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
14The University of Chicago Medical Center, Chicago, IL
15Royal Prince Alfred Hospital and Department of Medicine, The University of Sydney, Sydney, Australia
16Department of Hematology, Hospital Universitario Virgen del Rocio; Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla,Spain, Sevilla, Spain
17Oregon Health and Science University, Portland, OR
18Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
19University of Cologne, Cologne, Germany
20Lymphoma Unit, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano, Italy
21Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
22Department of Haematological Medicine, King’s College Hospital, London, United Kingdom
23Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwoon, KS
24Internal Medicine I, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria
25University Hospital Ghent, Gent, Belgium
26Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
27Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
28Cambridge University Hospitals NHS Foundation Trust, Cambridge, CA, United Kingdom
29Novartis Pharma AG, Basel, Switzerland
30Novartis Pharmaceuticals Corporation, East Hanover, NJ
31Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
32Klinikum Der Universität München-Grosshadern, Medizinische Klinik und Poliklinik III, München, Germany

Background: Follicular lymphoma is an indolent disease with a continuous relapsing pattern and typically requires multiple lines of therapy. Novel therapies such as tisagenlecleucel are being investigated to improve outcomes. Primary analysis of the single-arm, multicenter, Phase II ELARA trial in r/r FL demonstrated that tisagenlecleucel resulted in high overall (ORR) and complete response rates (CRR), and prolonged progression-free survival (PFS) at a median follow-up of 11 months (mo). Here, we report updated efficacy results from the overall population at a median follow-up of 17 mo, and a subgroup analysis of pts with high-risk disease from the ELARA trial (NCT03568461).

Methods: Eligible adult pts had histologically confirmed r/r FL (grades 1-3A) after ≥2 lines of therapy or had relapsed after autologous stem cell transplant. Bridging therapy was allowed and was followed by disease evaluation before tisagenlecleucel infusion. Pts received tisagenlecleucel (0.6-6×108 CAR+ viable T cells) after lymphodepleting chemotherapy (fludarabine [25 mg/m2] + cyclophosphamide [250 mg/m2] QD for 3 d or bendamustine [90 mg/m2] QD for 2 d). Endpoints included ORR, CRR, PFS, and duration of response (DOR). Descriptive efficacy subanalyses were performed for 9 high-risk subgroups, including prior hematopoietic stem cell transplant (HSCT), ≥5 prior lines of therapy, progression of disease within 24 mo from first immunochemotherapy (POD24), double-refractory disease, high Follicular Lymphoma International Prognostic Index (FLIPI) at study entry, high lactate dehydrogenase at baseline, high C-reactive protein (CRP) prior to infusion, radiological bulky disease (by GELF criteria), and high total metabolic tumor volume (TMTV; >510 cm3) at baseline (median 155.32 cm3; range 0.1-2470.4 cm3). Descriptive subgroup analysis was supported by multivariate analysis to identify factors predictive of worse outcomes.

Results: As of March 29, 2021, 97 pts received tisagenlecleucel and 94 were evaluable for primary efficacy analysis (median follow-up 17 mo). High and durable responses were seen in the overall ELARA population (ORR 86.2%, CRR 69.1%, 9-mo DOR 76.0%, and 12-mo PFS 67.0%). In CR pts at 9 mo, PFS was 85.5% and estimated probability of remaining in response was 86.5%. Safety reflected known tisagenlecleucel profile; 48% of pts had CRS (majority were grade 1/2) and 11.3% had neurological events (3% grade ≥3). In the subgroup analysis, pts were stratified into risk groups. Efficacy (ORR, CRR) and durability of response were well maintained in all high-risk subgroups, except for POD24 (n=35), high TMTV (n=20), and ≥5 prior lines of therapy (n=27). Compared with corresponding low-risk subgroups, there was a numerical reduction in CRR for high-risk subgroups (POD24 59.0% vs 87.9%; high TMTV 40.0% vs 76.4%; ≥5 prior lines of therapy 59.3% vs 73.1%) (Figure). A reduction in 12-mo PFS was also identified for pts in these subgroups: POD24 (60.8% vs 77.9%), high baseline TMTV (54.5% vs 68.5%), and ≥5 prior lines of therapy (59.6% vs 69.7%). Evaluating the disease characteristics of the high TMTV subgroup compared with low TMTV, high TMTV was associated with a higher incidence of bulky disease (58.3% vs 90.0%), high FLIPI (54.2% vs 85.0%), and high CRP (45.8% vs 70.0%). In the multivariate analysis of high-risk factors, only POD24 (hazard ratio [HR] 2.34; 95% CI, 1.02- 5.34) and high TMTV (HR 2.53; 95% CI, 1.14-5.65) were associated with shorter PFS. For pts with both POD24 and high TMTV (n=12), the CRR was 16.7% with a 12-mo PFS of 36.0%. These analyses of high-risk subgroups are exploratory in nature and should be validated in a larger study cohort.

Conclusions: With 17-mo median follow-up, tisagenlecleucel produced high ORR and CRR and was associated with durable response and promising 12-mo PFS in pts with r/r FL and 2+ prior lines of therapy. Safety was consistent with known tisagenlecleucel profile. POD24 and high TMTV were independently associated with PFS. These results suggest that tisagenlecleucel can induce high rates of durable response, including most pts in the high-risk disease subgroups, who have poor prognosis with current non-CAR-T cell therapies.

Disclosures: Thieblemont: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: 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, Other: Travel, Accommodations, Expenses , Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Dickinson: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Celgene: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria. Martinez-Lopez: Incyte: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau. Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Popplewell: Pfizer: Other: Travel; Novartis: Other: Travel; Hoffman La Roche: Other: Food. Chavez: AstraZeneca: Research Funding; Novartis: Consultancy; MorphoSys: Speakers Bureau; Karyopharm Therapeutics: Consultancy; Adaptive: Research Funding; Kite/Gilead: Consultancy; Abbvie: Consultancy; Merck: Research Funding; BeiGene: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Speakers Bureau; Epizyme: Speakers Bureau. Bachy: Takeda: Consultancy; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Honoraria. Kato: Chugai: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Eisai: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding. Harigae: Kyowakirin: Other: Subsidies or Donations; Astellas Pharma: Other: Subsidies or Donations; Ono pharma: Honoraria, Other: Subsidies or Donations; Janssen Pharma: Honoraria; Chugai Pharma: Honoraria; Novartis Pharma: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Kersten: Roche: Honoraria; BMS/Celgene: Honoraria, Research Funding; Miltenyi Biotech: Honoraria; Novartis: Honoraria; Kite/Gilead: Honoraria, Research Funding; Takeda: Honoraria. Andreadis: GenMAB: Research Funding; Karyopharm: Honoraria; Incyte: Honoraria; BMS/Celgene: Research Funding; Epizyme: Honoraria; Crispr Therapeutics: Research Funding; Atara: Consultancy, Honoraria; Novartis: Research Funding; Kite: Honoraria; Merck: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; TG Therapeutics: Honoraria. Riedell: Kite/Gilead: Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; BeiGene: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calibr: Research Funding. Pérez-Simón: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Nastoupil: MorphoSys: Honoraria; Bayer: Honoraria; Genentech: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Novartis: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Epizyme: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Von Tresckow: Pentixafarm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; MSD: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: Congress and travel support; AstraZeneca: Honoraria, Other: Congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: Congress and travel support; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Teshima: Fuji pharma CO.,Ltd: Research Funding; Astellas Pharma Inc.: Research Funding; TEIJIN PHARMA Limited: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Pfizer Inc.: Honoraria; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Janssen Pharmaceutical K.K.: Other; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol Myers Squibb: Honoraria; Sanofi S.A.: Research Funding; Gentium/Jazz Pharmaceuticals: Consultancy. Patten: ASTRA ZENECA: Honoraria; ABBVIE: Honoraria; NOVARTIS: Honoraria; GILEAD SCIENCES: Honoraria, Research Funding; ROCHE: Research Funding; JANSSEN: Honoraria. McGuirk: Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Novartis: Research Funding; Bellicum Pharmaceuticals: Research Funding; Gamida Cell: Research Funding; Pluristem Therapeutics: Research Funding; EcoR1 Capital: Consultancy; Allovir: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding. Petzer: AppVie: Honoraria; Astra Zeneca: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Sandoz: Honoraria. Viardot: University Hospital of Ulm: Current Employment; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: 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. Zinzani: JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; SANDOZ: Other: Advisory board; MSD: Consultancy, Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; Incyte: Other, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; ADC Therap.: Other; GILEAD: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Malladi: Gilead Science: Consultancy; Gilead: Honoraria, Other: Travel support. Lobetti Bodoni: Spouse: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Celgene: Honoraria; Spouse: Harlcok Healthcare: Current holder of individual stocks in a privately-held company; Spouse: Takeda: Consultancy, Honoraria, Speakers Bureau; Spouse: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spouse: NHS: Ended employment in the past 24 months; Spouse: F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company; Gilead: Other: Travel sponsorship in June 2019; Novartis: Current Employment, Current equity holder in publicly-traded company. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Schuster: Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Loxo Oncology: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Alimera Sciences: Consultancy; Merck: Research Funding; Incyte: Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; TG Theraputics: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Dreyling: Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; BeiGene: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy; Amgen: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding.

*signifies non-member of ASH