Cilta-Cel Shows Promise in Earlier Lines of Treatment in Patients With Progressive Multiple Myeloma


Cohort A of the CARTITUDE-2 study is evaluating cilta-cel safety and efficacy in patients with multiple myeloma who received 1 to 3 prior lines of therapy.

In patients with progressive multiple myeloma after 1 to 3 prior lines of therapy, a single ciltacabtagene autoleucel (cilta-cel)infusion led to deepening and durable responses at 17.1 months follow-up in this difficult-to-treat population with a poor prognosis. This is according to the updated clinical data from Cohort A of the ongoing multicohort phase 2 CARTITUDE-2 study (NCT04133636).1

The data were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, which is taking place from June 3-7, 2022 in Chicago, by Hermann Einsele, MD, of Universitätsklinikum Würzburg in Germany.

In February, cilta-cel (CARVYKTI, Jansen Biotech, Legend Biotech), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, received FDA approval for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy.2

CARTITUDE-2 is evaluating the safety and efficacy of cilta-cel in various multiple myeloma settings including earlier lines. Cohort A of the study is evaluating cilta-cel safety and efficacy in patients with multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor and immunomodulatory agent, and who are lenalidomide-refractory and have had no prior exposure to BCMA-targeting agents.

As of January 2022 (median follow-up 17.1 months), 20 patients (65% male, median age 60) received a single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg)

post lymphodepletion. Safety and efficacy were assessed, and the primary end point was minimal residual disease (MRD) negativity at 10-5.

The overall response rate (ORR) was 95%, while 90% achieved a complete response

(CR) or better, and 95% had a very good partial response (VGPR) or better. The median times to first and best response were 1 month and 2.6 months, respectively. Of the patients, 16 were MRD-evaluable, all of whom achieved MRD negativity at 10-5. The median duration of response (DOR) was not reached and the 12-month event-free rate was 79%. The 12-month progression free survival (PFS) rate was 75%.

Meanwhile, the median time to onset of cytokine release syndrome was 7 days and it occurred in 95% of patients, with median duration of 3 days. The rates of neurotoxicity and immune effector cell-associated neurotoxicity syndrome (ICANS) were 30% and 15%, respectively, while 1 patient had grade 2 facial paralysis.

One death occurred due to COVID-19, while 2 were due to progressive disease, and 1 was due to sepsis that was unrelated to the treatment.

The updated data from the CARTITUDE-2 study “demonstrates the promise of cilta-cel in earlier lines of treatment,” said Ying Huang, PhD, chief executive officer of Legend Biotech.3

This patient population is being further evaluated in the CARTITUDE-4 study (NCT04181827).

For more coverage of ASCO 2022, click here.

1. Einsele H, Cohen A, Delforge M, et al.Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in lenalidomide (len)-refractory patients (pts) with progressive multiple myeloma (MM) after 1–3 prior lines of therapy (LOT): CARTITUDE-2, cohort A. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #8020
2. U.S. FDA Approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen’s First Cell Therapy, a BCMA-Directed CAR-T Immunotherapy for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. News release. Janssen Biotech. February 28,2022.
3. Legend Biotech to Highlight Continued Progress in the Treatment of Multiple Myeloma With Updated Data From BCMA CAR-T Studies at 2022 ASCO and EHA. News release. Legend Biotech. May 18, 2022.
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