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3354 Ciltacabtagene Autoleucel (Cilta-cel), a BCMA-Directed CAR-T Cell Therapy, in Patients with Multiple Myeloma (MM) and Early Relapse after Initial Therapy: CARTITUDE-2 Cohort B 18-Month Follow-up

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Biological therapies, clinical trials, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Niels WCJ Van De Donk, MD1, Mounzer Agha2, Adam D Cohen, MD3, Yael C Cohen4*, Sébastien Anguille5*, Tessa Kerre6*, Wilfried W.H. Roeloffzen, MD, PhD7*, Deepu Madduri, MD8*, Jordan M Schecter9, Kevin C De Braganca9*, Carolyn C Jackson9*, Helen Varsos9*, Pankaj Mistry10*, Tito Roccia11*, Xiaoying Xu9*, Katherine Li12*, Enrique Zudaire12, Christina Corsale9*, Muhammad Akram13*, Dong Geng13*, Lida Pacaud13*, Pieter Sonneveld, MD14 and Sonja Zweegman, MD, PhD1

1Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
2UPMC Hillman Cancer Center, Pittsburgh, PA
3University of Pennsylvania, Philadelphia, PA
4Tel Aviv Sourasky (Ichilov) Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Vaccine and Infectious Disease Institute, University of Antwerp, Edegem, Belgium, Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium
6Ghent University Hospital, Ghent, Belgium
7University Medical Center Groningen, Groningen, Netherlands
8Mount Sinai Medical Center, New York, NY
9Janssen Research & Development, Raritan, NJ
10Janssen Research & Development, High Wycombe, United Kingdom
11Janssen Global Services, Raritan, NJ
12Janssen Research & Development, Spring House, PA
13Legend Biotech USA, Piscataway, NJ
14Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands

Introduction: In cohort B of the multicohort phase 2 CARTITUDE-2 (NCT04133636) study, the efficacy and safety of cilta-cel are being evaluated in patients with multiple myeloma (MM) who had early relapse (≤12 months after autologous stem cell transplant [ASCT] or ≤12 months after start of initial treatment with anti-myeloma therapy). Because progression within 1 year of starting initial therapy is a poor prognostic factor, with overall survival <2 years in these patients, they have functionally high-risk disease and represent an unmet medical need. We present updated clinical results and cytokine analyses.

Methods: Eligible patients had MM, received 1 prior line of therapy (proteasome inhibitor and immunomodulatory drug required), had early disease progression (≤12 mo after ASCT or ≤12 mo after start of anti-myeloma therapy for patients who did not undergo ASCT), and were treatment-naive to CAR-T/anti-B-cell maturation antigen (BCMA) therapies. Bridging therapy was allowed between apheresis and CAR-T cell infusion. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was given post lymphodepletion. Safety and efficacy were assessed. The primary endpoint was minimal residual disease (MRD) negativity by next generation sequencing at 10-5. Management strategies were implemented to minimize risk of movement/neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism. Pharmacokinetics, CAR-T cell phenotype, and cytokine profiles are also being investigated.

Results: As of June 1, 2022, 19 patients (median age 58 years [range 44–67]; 74% male; 16% high-risk cytogenetics, 63.2% standard risk, 21.1% unknown) received cilta-cel and 16 remained on study. Median follow-up was 17.8 months (range 5.2–26.3). 79% of patients received prior ASCT. Overall response rate was 100%, with 100% achieving very good partial response or better, and 90% achieving complete response or better (Figure). Median time to first response and best response were 0.95 months (range 0.9 – 9.7) and 5.1 months (range 0.9 – 11.8), respectively. Of patients who were MRD-evaluable (n= 15), 14 (93 %) achieved MRD 10-5 negativity during the study. Median DOR was not reached and 12-month event-free rate was 84%. The 12-month progression-free survival rate was 90%. Most common treatment-emergent AEs were hematologic (grade 3/4: neutropenia, 90%; lymphopenia, 42%; thrombocytopenia, 26%; leukopenia, 26%). Median time from cilta-cel infusion to onset of cytokine release syndrome (CRS) was 8 days (range 5–11) and occurred in 16 (84.2%) patients (grade 4, n=1). CRS resolved in all patients. Immune effector cell-associated neurotoxicity syndrome (grade 1) occurred in 1 patient and Movement and neurocognitive TEAEs/parkinsonism (grade 3) occurred in 1 patient (previously reported). Three patients died post cilta-cel at days 158, 417, and 451 due to progressive disease. Levels of interleukin (IL)-6, interferon gamma, IL-2Rα, and IL-10 increased post infusion, peaked at days 7–14, coincident with the timing of CRS, and returned to baseline levels within 2–3 months post infusion.

Conclusions: In this functionally high-risk patient population, all of whom relapsed within a year of treatment with standard of care upfront therapy (including 79% with ASCT), 90% remained progression-free at 1 year post cilta-cel infusion. Results at this longer (18 months) follow-up show durability and deepening of response to cilta-cel and maintenance of PFS rate. This represents a potentially significant advancement in a population with high unmet need.

Disclosures: Van De Donk: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; 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; Bayer: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Agha: GenCART Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Cohen: Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Ichnos, Janssen Oncology, Oncopeptides, Pfizer, Seattle Genetics, Genentech/Roche, AstraZeneca, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline and Novartis: Research Funding; Novartis: Patents & Royalties: CAR T-cells and biomarkers of cytokine-release syndrome. Cohen: Medison: Honoraria; GSK: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; Neopharm: Honoraria. Roeloffzen: Amgen: Honoraria; Sanofi: Honoraria; Bristol Myers Squibb: Honoraria; Janssen: Honoraria. Madduri: Janssen: Current Employment; Amgen, Allogene, BMS, Celgene: Research Funding; BMS, Takeda, GSK, Kinevant, Legend, Sanofi, Celgene: Consultancy. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. De Braganca: Janssen R&D: Current Employment. Jackson: Janssen R&D: Current Employment. Varsos: Janssen: Current Employment. Roccia: Janssen: Current Employment, Current equity holder in publicly-traded company. Li: Janssen R&D, a Johnson and Johnson company: Current Employment, Current equity holder in publicly-traded company. Zudaire: Janssen R&D, Johnson and Johnson: Current Employment. Corsale: Janssen R&D: Current Employment. Geng: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech USA: Current Employment. Sonneveld: Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: 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, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Zweegman: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: 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, Research Funding.

OffLabel Disclosure: Cilta-cel is a CAR-T therapy approved for patients with relapsed/refractory multiple myeloma after 4 or more lines of therapy.

*signifies non-member of ASH