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Comparative Effectiveness Research for CAR-T Therapies in Multiple Myeloma: Appropriate Comparisons Require Careful Considerations of Data Sources and Patient Populations

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Abstract

Background and Objective

Registrational trials for ciltacabtagene autoleucel [cilta-cel]) and idecabtagene vicleucel [ide-cel] chimeric antigen receptor T-cell (CAR-T) therapies were single-arm studies conducted with relapse refractory multiple myeloma (MM) patients who were triple-class-exposed (TCE) or triple-class-refractory (TCR). It is critical for researchers conducting comparative effectiveness research (CER) to carefully consider the most appropriate data sources and comparable patient populations. The aim of this study was to identify potential data sources and populations for comparing to single-arm CAR-T trials CARTITUDE-1 (cilta-cel) and KarMMa (ide-cel).

Methods

A 2-part global systematic literature search produced a review of (1) clinical trials of National Comprehensive Cancer Network (NCCN) guideline preferred regimens in previously treated MM, and (2) real-world data cohorts of TCE or TCR populations, published between 1/1/2015 and 12/10/2020, with sample sizes of > 50 patients and reporting survival-related outcomes. Implications on CER and accepted best practices are discussed.

Results

Nine clinical trials of NCCN preferred regimens were identified along with five real-world data-based publications. No clinical trials evaluated patients with TCE or TCR MM. Among the real-world data-based publications, two evaluated patients exclusively with TCR MM, two analyzed a mixed population of patients with TCE or TCR MM, and one publication assessed patients exclusively with TCE MM. Real-world data treatment patterns were heterogeneous.

Conclusion

Current NCCN preferred regimens were not specifically studied in TCE or TCR MM patients, although some studies do include a proportion of these types of patients. Therefore, appropriate matching of populations using either real-world data or patient level clinical trial data is critical to putting trials of novel CAR-Ts (i.e., CARTITUDE-1 or KarMMa) into appropriate comparative context.

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Acknowledgements

The authors thank Mr. Nicholas Adair (Panalgo LLC) for his assistance with manuscript preparation and literature searches.

Author information

Authors and Affiliations

  1. University of California San Francisco, San Francisco, CA, USA

    Nina Shah

  2. Panalgo LLC, 265 Franklin Street, Suite 1101, Boston, MA, 02110, USA

    Matthew Sussman & Jennifer Benner

  3. Janssen Scientific Affairs LLC, Titusville, NJ, USA

    Concetta Crivera & Satish Valluri

  4. Mount Sinai, New York, NY, USA

    Sundar Jagannath

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  1. Nina Shah
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Corresponding author

Correspondence to Matthew Sussman.

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Funding

This research study was funded by Janssen Pharmaceuticals, Inc.

Conflict of interest

Nina Shah has received research funding from Bristol-Myers Squibb, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, and Nektar, and has undertaken an advisory role with GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, and Oncopeptides. Matthew Sussman and Jennifer Benner are employees of Panalgo LLC and were paid consultants in connection with the study. Concetta Crivera and Satish Valluri are employees of Johnson & Johnson (J & J) and have in excess of $10,000 of J & J stock. Sundar Jagannath is a consultant for Bristol-Myers Squibb, Karyopharm Therapeutics, Legend Biotech, Sanofi and Takeda.

Ethics approval

This study involved a systematic review of the literature and therefore did not require ethics approval.

Consent to participate

This study involved a systematic review of the literature and therefore did not require patient consent.

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Not applicable.

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This study involved a systematic review of the literature; therefore, all data and materials are publicly available.

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Appendices

Appendix 1: Search Criteria for Off-label Regimens

Bortezomib + lenalidomide + dexamethasone: ((bortezomib[mh] OR "bortezomib") AND ("lenalidomide" OR lenalidomide[mh]) AND ("dexamethasone" OR dexamethasone[mh]) AND (("relapsed" AND "refractory") AND ("multiple myeloma" OR multiple myeloma[mh]))

Ixazomib + pomalidomide + dexamethasone: ((ixazomib[Supplementary Concept] OR "ixazomib") AND ("pomalidomide" OR pomalidomide[Supplementary Concept]) AND ("dexamethasone" OR dexamethasone[mh]) AND (("relapsed" AND "refractory") AND ("multiple myeloma" OR multiple myeloma[mh]))

Pomalidomide + bortezomib + dexamethasone: ((bortezomib[mh] OR "bortezomib") AND ("pomalidomide" OR pomalidomide[Supplementary Concept]) AND ("dexamethasone" OR dexamethasone[mh]) AND (("relapsed" AND "refractory") AND ("multiple myeloma" OR multiple myeloma[mh]))

Appendix 2: Search Criteria for Full-text Real-world Data Evaluations of TCE or TCR Populations

Search criteria included: ("relapsed" OR "refractory" OR "triple-class" OR "quad-refractory" OR "penta-refractory") AND ("multiple myeloma" OR multiple myeloma[mh]) AND ("Progression-free survival" OR progression free survival[mh] OR "overall survival" OR "prognosis" OR "treatment patterns" OR "outcome" OR prognosis[mh] OR treatment outcome[mh]) AND (Observational study[mh] OR cohort studies[mh] OR "retrospective")

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Shah, N., Sussman, M., Crivera, C. et al. Comparative Effectiveness Research for CAR-T Therapies in Multiple Myeloma: Appropriate Comparisons Require Careful Considerations of Data Sources and Patient Populations. Clin Drug Investig 41, 201–210 (2021). https://doi.org/10.1007/s40261-021-01012-x

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