Clonal Myeloid Dysplasia Following CAR T-Cell Therapy: Chicken or the Egg?

Vladimir Vainstein*, Batia Avni, Sigal Grisariu, Shlomit Kfir-Erenfeld, Nathalie Asherie, Boaz Nachmias, Shlomtzion Auman, Revital Saban, Eran Zimran, Miri Assayag, Kalman Filanovsky, Netanel A. Horowitz, Eyal Lebel, Adir Shaulov, Michal Gur, Chaggai Rosenbluh, Svetlana Krichevsky, Polina Stepensky, Moshe E. Gatt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Multiple myeloma (MM) is characterized by recurrent relapses. Consequently, patients receive multiple therapy lines, including alkylating agents and immune modulators, which have been associated with secondary malignancies such as myelodysplastic syndrome (MDS). Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy is efficacious in patients with relapsed/refractory (R/R) MM. However, the long-term complications, particularly MDS, are not well understood. Whether CART therapy causes or promotes MDS has not been thoroughly investigated. In this study, we explored the causal relationship between MDS and CART therapy. We retrospectively examined the prevalence of MDS-related morphological and mutational changes before and after administration of CART therapy in five patients. Among them, four developed MDS after CART therapy, while one had pre-existing MDS prior to CART. None of the four patients who developed post-CART MDS showed morphological MDS changes prior to CART therapy. However, all four patients exhibited molecular alterations associated with MDS in their pre-CART as well as post-CART therapy bone marrow. No new mutations were observed. Our findings provide initial evidence suggesting that anti-BCMA CART therapy in MM may promote expansion of pre-existing MDS clones rather than causing development of new clones.

Original languageAmerican English
Article number3471
JournalCancers
Volume15
Issue number13
DOIs
StatePublished - 3 Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • CART therapy
  • multiple myeloma
  • myelodysplastic syndrome

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