Myelodysplastic Syndrome Secondary to Chimeric Antigen Receptor T-cell (CAR-T) Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma

TL;DR

A patient with multiple myeloma developed myelodysplastic syndrome after CAR-T therapy, highlighting potential long-term risks of this treatment.

Contribution

This case report highlights a novel association between CAR-T therapy and therapy-related myelodysplastic syndrome in multiple myeloma patients.

Findings

A patient developed MDS with a 7q deletion following CAR-T therapy for multiple myeloma.

The cytogenetic abnormality was not present in prior marrow evaluations.

The case suggests a possible link between CAR-T therapy and secondary hematologic malignancies.

Abstract

We present the case of a 65-year-old man with relapsed/refractory multiple myeloma (RRMM) who developed therapy-related myelodysplastic syndrome (MDS) following chimeric antigen receptor T-cell (CAR-T) therapy with idecabtagene vicleucel (ide-cel). The patient, initially diagnosed in 2019, underwent multiple lines of therapy, including high-dose melphalan with autologous stem cell transplantation, before receiving ide-cel for progressive disease. Despite initial remission, a day 100 bone marrow biopsy revealed MDS with a 7q deletion, a cytogenetic abnormality not present on prior marrow evaluations. While CAR-T therapy has revolutionized RRMM treatment, long-term complications such as therapy-related hematologic malignancy remain under-recognized.

The temporal relationship between CAR-T infusion and the emergence of a new therapy-induced cytogenetic abnormality raises concern for either CAR-T stress revealing a pre-existing myeloid clone or acceleration of therapy-induced myeloid neoplasia in a heavily pretreated patient. This case illustrates the need for standardized guidelines for malignancy screenings and long-term monitoring in CAR-T recipients. Further studies are essential to delineate the timing, mechanisms, and risk factors for secondary malignancies in CAR-T recipients.

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