CAR T cell therapy for multiple myeloma: What have we learned?

Susanibar-Adaniya, Sandra P.; Stadtmauer, Edward A.; Cohen, Adam D.

doi:10.1038/s41375-022-01539-8

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…In addition, lymphodepleting regimen may enhance the expansion of adoptively transferred T cells leading to superior persistence ( 130 ). First, lymphocytes depletion therapy before CAR-T could greatly reduce the risk of anti-CAR immune response.…”

Section: Strategies To Improve the Efficacymentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy for multiple myeloma

et al. 2022

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Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients, as persistent clonal evolution drives new mutations which confer MM high-risk signatures and resistance to standard care. The past two decades have significantly refashioned the therapeutic options for MM, especially adoptive T cell therapy contributing to impressive response rate and clinical efficacy. Despite great promises achieved from chimeric antigen receptor T-cell (CAR-T) therapy, the poor durability and severe toxicity (cytokine release syndrome and neurotoxicity) are still huge challenges. Therefore, relapsed/refractory multiple myeloma (RRMM), characterized by the nature of clinicopathologic and molecular heterogeneity, is frequently associated with poor prognosis. B Cell Maturation Antigen (BCMA) is the most successful target for CAR-T therapy, and other potential targets either for single-target or dual-target CAR-T are actively being studied in numerous clinical trials. Moreover, mechanisms driving resistance or relapse after CAR-T therapy remain uncharacterized, which might refer to T-cell clearance, antigen escape, and immunosuppressive tumor microenvironment. Engineering CAR T-cell to improve both efficacy and safety continues to be a promising area for investigation. In this review, we aim to describe novel tumor-associated neoantigens for MM, summarize the data from current MM CAR-T clinical trials, introduce the mechanism of disease resistance/relapse after CAR-T infusion, highlight innovations capable of enhanced efficacy and reduced toxicity, and provide potential directions to optimize manufacturing processes.

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Section: Strategies To Improve the Efficacymentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy for multiple myeloma

et al. 2022

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BCMA CAR-T cells in multiple myeloma–ready for take-off?

Scheller,

Tebuka,

Rambau

et al. 2023

Leukemia & Lymphoma

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CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

Marhelava

Krawczyk

Firczuk

et al. 2022

Cells

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Chimeric antigen receptor (CAR)-T cell therapy is undeniably a promising tool in combating various types of hematological malignancies. However, it is not yet optimal and a significant number of patients experience a lack of response or relapse after the treatment. Therapy improvement requires careful analysis of the occurring problems and a deeper understanding of the reasons that stand behind them. In this review, we summarize the recent knowledge about CAR-T products’ clinical performance and discuss diversified approaches taken to improve the major shortcomings of this therapy. Especially, we prioritize the challenges faced by CD19 CAR-T cell-based treatment of B cell-derived malignancies and revise the latest insights about mechanisms mediating therapy resistance. Since the loss of CD19 is one of the major obstacles to the success of CAR-T cell therapy, we present antigens that could be alternatively used for the treatment of various types of B cell-derived cancers.

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CAR T cell therapy for multiple myeloma: What have we learned?

Cited by 3 publications

References 26 publications

Chimeric antigen receptor T-cell therapy for multiple myeloma

Chimeric antigen receptor T-cell therapy for multiple myeloma

BCMA CAR-T cells in multiple myeloma–ready for take-off?

CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

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