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Cited by 90Multiple Myeloma Research and TreatmentsCAR-T cell therapy researchMultiple Sclerosis Research Studies

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma

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Jagannath, Sundar, Lin, Yi, Goldschmidt, Hartmut, Reece, Donna, Nooka, Ajay, Senin, Alicia, Rodriguez-Otero, Paula, Powles, Ray +9 more·2021·Blood Cancer Journal
DOI 10.1038/s41408-021-00507-2PMC PMC8213772
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Abstract

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.

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Crossref · 10.1038/s41408-021-00507-2

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  • In the KarMMa study involving 128 RRMM patients, the ORR to a single infusion of Abecma was 73%, with a CR rate of 33%.

    “In the KarMMa study involving 128 patients with RRMM, the overall response rate (ORR) to a single infusion of Abecma was 73%, with a complete response (CR) rate of 33%.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [258]

    The Results (Patients; page unavailable) identify 128 ide-cel-treated patients from KarMMa. But the Results (Overall response rate; page unavailable) report an adjusted ORR of 76.4%, not 73%, and do not report a 33% complete-response rate; the table notes that complete response was not reported because biopsy data were missing in the real-world comparator cohort. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The median duration of response to Abecma was 11 months in patients achieving CR and 19 months in those achieving sCR.

    “The median duration of response (mDOR) was 11 months in patients achieving CR and 19 months in those achieving stringent complete response (sCR).”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [258]

    The Results section, “Duration of response and time to response” (page unavailable), reports a median DOR of 11.1 months for the overall ide-cel–treated KarMMa cohort, not specifically for patients achieving CR. It does not report a 19-month median DOR for patients achieving sCR. Thus, only the approximate 11-month figure is supported, and its stated subgroup is not. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Chimeric antigen receptor T-cell therapy has shown promising efficacy in patients with triple-class-exposed relapsed and refractory multiple myeloma.

    “Chimeric antigen receptor (CAR) T-cell therapy has shown promising ef fi cacy in patients with TCE R/RMM. 13-21”

    From Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (2024) · cites this paper as [20]

  • Common side effects of Abecma such as CRS and ICANS were mostly low grade.

    “Common side effects such as CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were mostly low grade, indicating manageable toxicity.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [258]

  • Abecma has demonstrated the ability to induce rapid, deep, and long-lasting remissions with just one infusion.

    “Abecma has demonstrated the ability to induce rapid, deep, and long-lasting remissions with just one infusion, providing a new and effective personalized therapy option for MM patients [227, 243, 258, 259].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [258]

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Research works printed but not linked: 25

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Authors
Jagannath, S., Lin, Y., Goldschmidt, H., Reece, D., Nooka, A., Senin, A., Rodriguez-Otero, P., Powles, R., Matsue, K., Shah, N., Anderson, L. D., Streetly, M., Wilson, K., Le, H. V., Swern, A. S., Agarwal, A., & Siegel, D. S.
Affiliations
  • Mount Sinai Hospital (US)
  • Mayo Clinic (US)
  • University Hospital Heidelberg (DE)
  • Princess Margaret Cancer Centre (CA)
  • Emory University (US)
  • Kameda Medical Center (JP)
  • University of California, San Francisco (US)
  • Harold C. Simmons Comprehensive Cancer Center (US)
  • Guy's Hospital (GB)
  • Bristol-Myers Squibb (United States) (US)
  • Hackensack University Medical Center (US)
Corresponding author
Jagannath, Sundar
ORCID
Venue
Blood Cancer Journal
Publisher
Springer Science and Business Media LLC
Published
2021-06-18
Volume
11
Issue
6
Pages
116-116
ISSN
2044-5385 (ISSN-L)
DOI
10.1038/s41408-021-00507-2
PMC
PMC8213772
OpenAlex
W3168326299
Cited by
90
References
6
Citations by year
2026: 12 · 2025: 16 · 2024: 20 · 2023: 20 · 2022: 18 · 2021: 4
FWCI
10.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Blood Cancer Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
Celgene, a Bristol-Myers Squibb Company and bluebird bio
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
idecabtagene vicleucel, relapsed/refractory multiple myeloma, BCMA CAR T-cell therapy, real-world outcomes, immunomodulators, proteasome inhibitors, anti-CD38 monoclonal antibody, progression-free survival, overall survival, overall response rate
MeSH terms
Receptors, Chimeric Antigen, Progression-Free Survival, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Middle Aged, Multiple Myeloma, Retrospective Studies, Survival Rate, Immunotherapy, Adoptive, Drug Resistance, Neoplasm

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