A recent case study highlighted the emergence of myelodysplastic syndromes (MDS) as a potential long-term consequence of CD19-targeted chimeric antigen receptor-modified T-cell (CAR-T cell) immunotherapy.
The patient, a 53-year-old female, underwent CAR-T therapy for non-Hodgkin lymphoma after multiple relapses. Following the successful CAR-T treatment with tisagenlecleucel, the patient achieved a complete metabolic response. However, in the months that followed, she experienced recurrent episodes of neutropenia, which eventually worsened to a grade III level.
Subsequent investigations through next-generation sequencing revealed chromosomal abnormalities, including a monosomy of chromosome 7 and a DNMT3A mutation, leading to the diagnosis of MDS.
“Our case highlights two important points: [1] Patients with prolonged cytopenias after CAR T-cells should be investigated and monitored for a longer time, even after 90 days from infusion, because such cytopenias may represent an initial MDS phase; [2] cytogenetic and next generation sequencing information should be obtained before CAR-T infusion and after the procedure with longitudinal monitoring, especially in non-Hodgkin lymphoma patients that previously received 3 or more lines of treatment,” the study’s authors wrote in a letter to the editor of Annals of Hematology.
Read more about MDS complications
This case raises concerns about the potential long-term consequences of CAR-T therapy, specifically, the development of MDS, which can emerge months after the procedure. Hence, patients experiencing prolonged cytopenias following CAR-T therapy should be closely monitored for signs of MDS.
Moreover, the study calls for further prospective research to explore the relationship between CAR-T therapy, previous treatments, and the development of MDS as a late event. As CAR-T therapy continues to revolutionize cancer treatment, a comprehensive understanding of potential long-term effects is essential for optimizing patient care and outcomes.
Reference
Di Rocco A, Di Palma M, D’Elia GM, et al. Myelodysplastic clones arising post chimeric antigen receptor t cell therapy (car-t) procedure: a casuality or a new entity? Ann Hematol. Published online July 19, 2023. doi:10.1007/s00277-023-05329-9
