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Ide-cel: EC approval and updated results from KarMMa

Aug 19, 2021
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In March 2021, idecabtagene vicleucel  (ide-cel) became the first B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsed/refractory (R/R) multiple myeloma (MM). On August 20, 2021, the European Commission (EC) granted ide-cel conditional marketing authorization for the treatment of adult patients with R/R MM who have received ≥3 prior lines of therapy.1 

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Larry Anderson, UT Southwestern Medical Center, Fort Worth, US, provided an update of the long-term analysis of the KarMMa trial (NCT03361748); a phase II study that facilitated the approvals. The Multiple Myeloma Hub is happy to provide an update.

Study design2,3 

A key objective of the long-term analysis was to evaluate the safety and efficacy of ide-cel with respect to number of prior lines of therapy (3 vs ≥4). The initial KarMMa study design (Figure 1) included patients who had received ≥3 prior lines of therapy, however the U.S. Food and Drug Administration (FDA) indication necessitates data from patients who have undergone ≥4 prior lines of therapy.2 

Figure 1. KarMMa trial design*

CAR, chimeric antigen receptor; Cy, cytarabine; Flu, fludarabine; Ide-cel, idecabtagene vicleucel; IMiD, immunomodulatory agent; IMWG, International Myeloma Working Group; PD, progressive disease; PI, proteasome inhibitor; RRMM, relapsed or refractory multiple myeloma.
*Adapted from Shah.3

Results2

  • Data cutoff: December 21, 2020.
  • Median follow-up 24.8 months.
  • Baseline characteristics were similar between patients who had received 3 vs ≥4 prior lines of therapy, but numerical differences were observed in
    • Extramedullary disease
    • High-risk cytogenetics
    • Prior refractoriness
    • Time since initial diagnosis to screening

Efficacy

  • Updated efficacy data among all ide-cell treated patients are outlined in Table 1.
  • Response rates were comparable between patients who had received 3 vs ≥4 prior lines of therapy (Figure 2).

Table 1. Efficacy of ide-cel across all CAR+ T-cell target doses*

Response

All ide-cel treated patients (N = 128)

ORR, %

73

CR/sCR, %

33

Median DOR, months

10.9

Median PFS, months

8.6

Median OS, months

24.8

CAR, chimeric antigen receptor; CR, compete response; DOR, duration of response; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; sCR, stringent CR.
*Data from Anderson et al.2

Figure 2. ORRs to ide-cel by number of prior lines of therapy*

CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Adapted from Anderson et al.2

Safety

  • Incidences of adverse events, including cytokine release syndrome and neurotoxicity, were consistent with previous findings, and were comparable between patients who received 3 vs ≥4 prior lines of therapy.

Conclusions

The safety and efficacy profiles of ide-cel were consistent with previously reported data, and ide-cel demonstrated promising outcomes in patients with heavily pretreated MM, irrespective of number of prior lines of therapy and risk profile.

Additional resources

Follow the links for more information on the ongoing trials evaluating ide-cel for MM and a review on the impact of CAR T-cell therapy on quality of life in patients with triple-class refractory MM.

  1. Bristol Myers Squibb. Bristol Myers Squibb receives European Commission approval for Abecma (idecabtagene vicleucel), the first anti-BCMA CAR T cell therapy for relapsed and refractory multiple myeloma. https://news.bms.com/news/details/2021/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-Abecma-Idecabtagene-Vicleucel-the-First-Anti-BCMA-CAR-T-Cell-Therapy-for-Relapsed-and-Refractory-Multiple-Myeloma/default.aspx. Published August 19, 2021. Accessed August 20, 2021. 
  2. Anderson LD, Munshi NC, Shah N, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: Updated KarMMa results. Poster #8016. 2021 ASCO Annual Meeting; June 4−8, 2021; Virtual.
  3. Nina Shah. Secondary quality-of-life domains in patients with relapsed and refractory multiple myeloma treated with the BCMA-directed CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121): results from the KarMMa clinical trial. Oral abstract 437. 62nd ASH Meeting and Exposition; Dec, 2020; Virtual.

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