MM-181 CARTITUDE-1: Two-Year Post Last Patient in (LPI) Results From the Phase 1b/2 Study of Ciltacabtagene Autoleucel (Cilta-Cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

Saad Z. Usmani, Thomas Martin, Jesus G. Berdeja, Andrzej Jakubowiak, Mounzer Agha, Adam D. Cohen, Abhinav Deol, Myo Htut, Alexander Lesokhin, Nikhil C. Munshi, Elizabeth O'Donnell, Carolyn C. Jackson, Tzu min Yeh, Arnob Banerjee, Enrique Zudaire, Deepu Madduri, Changwei Zhou, Lida Pacaud, Yi Lin, Sundar Jagannath

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Cilta-cel, a CAR-T cell therapy with 2 BCMA–targeting single-domain antibodies, led to early, deep, and durable responses in heavily pretreated patients with RRMM in the phase 1b/2 CARTITUDE-1 study (NCT03548207). Objective: To report updated results from CARTITUDE-1. Data 2-years post LPI (~30-month median follow-up [MFU]) will be presented; here we report results at 21.7-month MFU. Patients: Eligible patients with RRMM had ≥3 prior lines of therapy (LOT) or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody. Intervention: After apheresis, bridging therapy was allowed. A single infusion of cilta-cel (target dose 0.75×106 CAR+ viable T cells/kg) was administered 5–7 days after lymphodepletion. Main Outcome Measures: Cilta-cel safety and efficacy were the primary objectives. Assessments included response (per IMWG criteria by independent review committee) and minimal residual disease (MRD) negativity (at 10-5 by next-generation sequencing). Results: As of July 22, 2021, 97 patients (59% male; median age 61 years; median 6 [range 3–18] prior LOT) received cilta-cel. Overall response rate was 97.9% (94.9% very good partial response; 82.5% stringent complete response). Median times to first response, best response, and ≥complete response were 1.0, 2.6, and 2.9 months, respectively. Median duration of response was not reached. Among 61 MRD-evaluable patients, 92% were MRD negative (10-5), sustained for ≥6 months in 44% and ≥12 months in 18%. Progression-free survival (PFS) at 2 years was 60.5%. Median PFS and overall survival were not reached. PFS rates at 2 years in patients with MRD negativity sustained for ≥6 months and ≥12 months were 91% and 100%, respectively. No new safety signals, new events of CAR-T cell neurotoxicity, movement and neurocognitive treatment-emergent adverse events, or treatment-related deaths have occurred since 1-year MFU. Over ~2 years MFU, 15 second, primary malignancies were reported in 11 patients. Conclusions: At ~2 years MFU, a single infusion of cilta-cel resulted in deepening and durable responses and manageable safety in heavily pretreated patients with RRMM. Additional research is ongoing to evaluate cilta-cel in earlier LOT and outpatient settings across the CARTITUDE program (NCT04133636, NCT04181827, NCT04923893).

Original languageEnglish (US)
Pages (from-to)S410-S411
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • CAR-T cell therapy
  • cilta-cel
  • MM
  • multiple myeloma
  • Phase I/II

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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