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3866 Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-Cell Maturation Antigen (BCMA)–Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma after 1–3 Prior Lines of Therapy: Updated Results from CARTITUDE-2

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Clinical: Poster III
Hematology Disease Topics & Pathways:
Biological, Clinical Trials, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, Therapies, Infusion, Lymphoid Malignancies
Monday, December 13, 2021, 6:00 PM-8:00 PM

Yael C. Cohen1*, Adam D Cohen, MD2, Michel Delforge, MD, PhD3*, Jens Hillengass, MD, PhD4, Hartmut Goldschmidt, MD5,6, Katja Weisel7*, Marc-Steffen Raab, MD8*, Christof Scheid9, Jordan M. Schecter10, Kevin C. De Braganca10*, Helen Varsos10*, Tzu-min Yeh10*, Liwei Wang10*, Martin Vogel11*, Christina Corsale11*, Muhammad Akram12*, Lida Pacaud12*, Tonia Nesheiwat12*, Mounzer Agha13 and Hermann Einsele14

1Tel-Aviv Sourasky (Ichilov) Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
2Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
3University Hospitals (UZ) Leuven, Leuven, Belgium
4Roswell Park Comprehensive Cancer Center, Buffalo, NY
5University Hospital Heidelberg, Heidelberg, Germany
6Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany
7University Medical Center Hamburg-Eppendorf, Hamburg, Germany
8University Hospital Heidelberg and Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany
9University of Cologne, Cologne, Germany
10Janssen R&D, Raritan, NJ
11Janssen Global Services, LLC., Raritan, NJ
12Legend Biotech USA, Piscataway, NJ
13UPMC Hillman Cancer Center, Pittsburgh, PA
14Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany

Introduction: There are several treatment options for patients (pts) with progressive multiple myeloma (MM) who are refractory to lenalidomide but most pts relapse shortly after receiving salvage treatment. Cilta-cel is a CAR-T therapy expressing 2 BCMA-targeting, single-domain antibodies that demonstrated early, deep, and durable responses in pts with MM who had received ≥3 prior lines of therapy (LOT) in the phase 1b/2 CARTITUDE-1 study (Berdeja, Lancet, 2021). The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for pts with MM and exploring suitability of outpatient administration. Initial analysis (median follow-up 5.8 mo) of pts in CARTITUDE-2 cohort A (lenalidomide-refractory with 1–3 prior LOT) demonstrated an overall response rate (ORR) of 95%, with 75% of pts achieving complete response or better (≥CR) and 85% achieving very good partial response or better (≥VGPR). Here, we present updated results for this population.

Methods: Pts had progressive MM after 1–3 prior LOT, including a PI and immunomodulatory drug (IMiD), were lenalidomide-refractory, and had no prior exposure to BCMA-targeting agents. Bridging therapy was allowed after apheresis. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was given 5–7 d after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 d). The primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints were ORR, duration of response (DOR), time and duration of MRD negativity, and incidence and severity of AEs. MRD was assessed by next-generation sequencing, response was assessed per IMWG criteria, and adverse events (AEs) were graded using CTCAEv5.0 (CRS and ICANS by ASTCT).

Results: Initial results from this cohort were published at ASCO 2021. Here we report data as of the April 15, 2021, data cutoff (median follow-up 9.7 mo: range 3.3–13.4). 20 pts (65% male; median age 60 years [range 38–75]) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (range 1–3); 60% received 1 or 2 prior LOT and 40% received 3 prior LOT. All pts were exposed to a PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. In all, 95% of pts were refractory to the last LOT; 40% were triple-class refractory. ORR was 95% (95% CI 75.1–99.9); 85% (95% CI 62.1–96.8) of pts had ≥CR, and 95% (95% CI 75.1–99.9) had ≥VGPR (Figure). Median time to first response was 1.0 mo (range 0.7–3.3); median time to best response was 3.3 mo (range 0.9–7.9); median time to ≥CR was 2.6 mo (range 0.9–7.9). Median DOR was not reached; 6-mo PFS rate was 90% (95% CI 65.6–97.4). Of MRD-evaluable pts (n=13), 92.3% (95% CI 64.0–99.8) were MRD-negative at 10-5. Hematologic AEs in ≥20% of pts were neutropenia (95%; grade [gr] 3/4: 95%), thrombocytopenia (80%; gr 3/4: 35%), anemia (75%; gr 3/4: 45%), lymphopenia (65%; gr 3/4: 60%) and leukopenia (55%; gr 3/4: 55%). CRS occurred in 95% of pts (gr 3/4: 10%). Median time to CRS onset was 7 d (range 5–9), with a median duration of 4 d (range 2–11). CRS resolved within 7 d in 90% of pts. CAR T-cell neurotoxicity occurred in 4 pts (20%; all gr 1/2). Three pts (15%) had ICANS (all gr 1/2); median time to onset was 8 d (range 7–10) and median duration was 3 d (range 1–3). One pt had other neurotoxicities (gr 2 facial paralysis); time to onset was 29 d with a duration of 51 d. No movement and neurocognitive TEAEs were observed. One death occurred due to COVID-19 (assessed as treatment-related by the investigator). Safety profile was manageable in the pt treated in an outpatient setting.

Conclusions: At a longer median follow-up of 9.7 mo, a single cilta-cel infusion led to early and deep responses in pts with MM who had 1–3 prior LOT and were lenalidomide-refractory. ORR in this cohort was consistent with the CARTITUDE-1 study in heavily pretreated pts; responses deepened over time, with 92% of MRD-evaluable pts achieving MRD 10-5 negativity. The safety profile was manageable; CRS was mostly gr 1/2, and no movement and neurocognitive TEAEs occurred, suggesting the efficacy of monitoring and pt management strategies that were implemented across phase 2/3 studies in the CARTITUDE program. Follow-up is ongoing, including additional enrollment in this cohort; this pt population is being further evaluated in the CARTITUDE-4 study (NCT04181827).

Disclosures: Cohen: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Research Funding; neopharm / promedico: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cohen: Janssen: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; BMS/Celgene: Consultancy; Novartis: Research Funding; Oncopeptides: Consultancy; Genentech/Roche: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Hillengass: Adaptive: Membership on an entity's Board of Directors or advisory committees; Beijing Medical Award Foundation: Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Beijing Life Oasis Public Service Center: Speakers Bureau; Curio Science: Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Skyline: Membership on an entity's Board of Directors or advisory committees. Goldschmidt: GSK: Honoraria; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raab: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Sanofi: 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; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid: BMS: 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; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. De Braganca: Janssen: Current Employment. Varsos: Janssen: Current Employment. Yeh: Janssen: Current Employment. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Corsale: Janssen: Current Employment. Akram: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding.

OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved.

*signifies non-member of ASH