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2028 Efficacy and Safety of Cilta-Cel in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Clinical Research, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, therapy sequence, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Adam D Cohen, MD1, María-Victoria Mateos2, Yael C Cohen3*, Paula Rodriguez Otero4*, Bruno Paiva4*, Niels WCJ Van De Donk, MD5, Thomas Martin, MD6, Attaya Suvannasankha, MD7*, Deepu Madduri, MD8*, Christina Corsale9*, Jordan M Schecter9, Kevin C De Braganca9*, Carolyn C Jackson9*, Helen Varsos9*, William Deraedt10*, Tito Roccia11*, Pankaj Mistry12*, Xiaoying Xu9*, Katherine Li13*, Enrique Zudaire13, Muhammad Akram14*, Lida Pacaud14*, Irit Avivi, MD15* and Jesús San-Miguel, MD, PhD4

1University of Pennsylvania, Philadelphia, PA
2Hospital Clinico Universitario de Salamanca, Salamanca, Spain
3Tel-Aviv Sourasky (Ichilov) Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4University of Navarra, Pamplona, Spain
5Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
6UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
7Indiana University Simon Cancer Center, Indiana University and Roudebush VAMC, Indianapolis, IN
8Mount Sinai Medical Center, New York, NY
9Janssen Research & Development, Raritan, NJ
10Janssen Research & Development, Beerse, Belgium
11Janssen Global Services, Raritan, NJ
12Janssen Research & Development, High Wycombe, United Kingdom
13Janssen Research & Development, Spring House, PA
14Legend Biotech USA, Piscataway, NJ
15Division of Hematology, Tel Aviv University, Tel Aviv, Israel

Introduction: With the availability of multiple therapy classes targeting BCMA for multiple myeloma (MM), data are needed to understand effective treatment (tx) sequencing. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of cilta-cel, an anti-BCMA CAR-T therapy, in several MM patient populations. We present updated results with a longer follow-up on cohort C patients with previous exposure to a non-cellular anti-BCMA immunotherapy.

Methods: Cohort C patients had progressive MM after tx with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was administered 5–7 days post lymphodepletion. The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints included overall response rate (ORR; assessed by IMWG criteria), duration of response (DOR), and adverse events (AEs).

Results: As of June 1, 2022, 20 patients (13-ADC exposed; 7 BsAb exposed; 1 patient in the ADC group also had prior BsAb exposure) were treated with cilta-cel. Four patients did not receive cilta-cel due to either low cellular yield (n=2, 1 patient in each group) or death due to progressive disease (PD) prior to dosing (n=2, 1 patient in each group). Six patients (30%) received anti-BCMA tx as their last line of therapy (LOT; n=4 ADC, n=2 BsAb). During prior anti-BCMA tx, best responses included very good partial response (VGPR; 2 patients in ADC group, 1 patient in BsAb group), stringent complete response (sCR, 1 patient in ADC group), and complete response (CR; 1 patient in BsAb group); the rest had best response of stable disease (SD) or PD (1 patient was not evaluable [NE]). At baseline, median age was 62.5 y (range, 44–81), 60% were male, 3 (15%) had high risk cytogenetics (all del17p), and 5 (25%) had baseline extramedullary disease. Patients had received a median of 8 (range, 4–13) prior LOT; 18 (90%) were triple-class refractory, 11 (55%) penta-drug refractory, and 16 (80%) refractory to non-cellular anti-BCMA treatment (Figure 1A). The median time from last anti-BCMA agent to cilta-cel infusion was 195 d (range, 62–749). Median administered dose of cilta‑cel was 0.65x106 (range, 0.21x106– 1.11x106) CAR+ viable T cells/kg; 1 patient received a below-target dose. At a median follow-up of 18.0 mo (range, 0.6–22.7), 7 of 10 evaluable patients (70%) were MRD-negative at 10-5 (5 of 7 evaluable patients [71.4%] in the ADC group, and 2 of 3 evaluable patients [66.7%] in the BsAb group). The ORR was 60% (95% CI, 36.1 – 80.9) for the full cohort (61.5% [95% CI, 31.6–86.1] in the ADC group and 57.1% [95% CI, 18.4–90.1] in the BsAb group; Figure 1B). Median DOR (95% CI) was 12.8 mo (7.9–NE) in the full cohort, 12.8 mo (7.9–NE) in the ADC group, and 8.2 mo (4.4–NE) in the BsAb group. Median PFS (95% CI) was 9.1 (1.5–13.8) mo in the full cohort, 9.5 mo (1.0–15.2) in the ADC group, and 5.3 mo (0.6–NE) in the BsAb group. Patients who responded to cilta-cel had a shorter median duration of last anti-BCMA agent exposure (29.5 d, range 1–277) compared with non-responders (63.5 d, range 54–260). Responders also had a longer median time from last anti-BCMA tx exposure to apheresis (161.0 d, range 26–695) than non-responders (56.5 d, range 40–77). The most common AEs were hematologic. CRS occurred in 12 (60%) patients (all grade 1/2), with median time to onset of 7.5 d (range, 2–10) and median duration of 6.0 d (3–10). ICANS occurred in 4 (20%) patients (2 grade 3/4), with median time to onset of 9.0 d (range, 4–13) and median duration of 7.0 d (range, 4–20). ICANS was recovered or resolved in 3 patients. No patient had movement or neurocognitive tx emergent AE/parkinsonism. There were 12 deaths: 8 due to PD, 2 due to COVID-19 pneumonia (not tx related), and 1 each due to subarachnoid hemorrhage (not tx related) and C. difficile colitis (tx related).

Conclusions: Heavily pretreated MM patients with previous exposure to a non-cellular anti-BCMA therapy had favorable responses following cilta-cel. However, depth and DOR appear lower than that seen in anti-BCMA-naïve patients treated with cilta-cel (at 27.7 mos, median DOR was not reached in heavily pre-treated but anti-BCMA naïve CARTITUDE-1 patients). These results may inform tx plans, including sequencing and washout period between BCMA-targeting agents.

Figure 1: (A) Patient Demographics and Disease Characteristics, (B) ORR

Disclosures: 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. Mateos: Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides, Seagen: Honoraria; Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Cohen: Medison: Honoraria; GSK: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; Neopharm: Honoraria. Rodriguez Otero: Janssen, BMS, Sanofi, Pfizer, GSK.: Consultancy; Hematology Clínica Universidad de Navarra: Current Employment; Amgen, Sanofi, GSK, Janssen, BMS-Celgene, Regeneron: Speakers Bureau; BMS-Celgene: Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Speakers Bureau; Amgen: Speakers Bureau; GSK: Consultancy, Speakers Bureau; Pfizer: Consultancy; Sanofi: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; BMS: Consultancy. Paiva: Adaptive: Honoraria; Takeda: Honoraria, Research Funding; GSK: Honoraria, Research Funding; EngMab: Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Roche Glycart AG: Honoraria, Research Funding; Amgen: Honoraria; Gliead: Honoraria; Oncopeptides: Honoraria. Van De Donk: Novartis: 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; 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; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: 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. Martin: Amgen, Johnson & Johnson / Janssen, Sanofi, and Seattle Genetics: Research Funding; GlaxoSmithKline and Legend Biotech: Consultancy; Legend Biotech: Consultancy. Suvannasankha: Regeneron: Research Funding; Sutro Biopharma: Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Janssen Oncology: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Madduri: BMS, Takeda, GSK, Kinevant, Legend, Sanofi, Celgene: Consultancy; Janssen: Current Employment; Amgen, Allogene, BMS, Celgene: Research Funding. Corsale: Janssen R&D: Current Employment. 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. Deraedt: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. 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. Pacaud: Legend Biotech USA: Current Employment. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. San-Miguel: Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Takeda, Regeneron, Roche, Sanofi, and SecuraBio: Consultancy, Other: Advisory Board.

*signifies non-member of ASH