Call to watch for rare secondary blood cancer after CAR T-cell therapy
13 February 2025
New research led by Peter Mac clinicians will potentially change the way cancer patients are monitored after receiving breakthrough CAR T-cell therapy.
A new paper, published in the New England Journal of Medicine, describes two patients who developed a rare blood cancer as a side-effect following CAR T-cell for multiple myeloma.
Professor Simon Harrison says these cases represent a “newly identified class-wide safety signal” for CAR T-cell therapy, and this should prompt a rethink of how patients are monitored after CAR T-cell therapy.
“These cases of secondary blood cancer are rare and have occurred in less than one percent of patients who received CAR T-cell therapy,” Professor Harrison, Director of the Centre of Excellence for Cellular Immunotherapy at Peter Mac, said.
“CAR-T therapy has proven to be highly effective in the treatment of blood cancer with the benefits of this therapy continuing to far outweigh any risk to patients with multiple myeloma. However, vigilant monitoring is required to keep watch for this secondary cancer in the longer term.”
The two patients, one located in Australian and the other in France, received CAR T-cell therapy as part of the CARTITUDE-4 clinical trial before developing T-Cell Lymphoma months after their treatment.
Through comprehensive genomic characterisation using cutting-edge technologies, teams at Peter Mac, the Wilson Centre for Blood Cancer Genomics and the Collaborative Centre for Genomic Cancer Medicine were able to dissect the origins of the lymphoma showing that it arose inside a CAR T-cell and was derived from cells present in the patient years previously.
Associate Professor Piers Blombery said: “the use of novel genomic techniques to investigate the lymphoma cells in these patients have let us understand where they are coming from, how to detect them at earlier stages and ultimately how to avoid them.”
Both patients responded well to further treatment for T-Cell Lymphoma, and their multiple myeloma has remained controlled.
The NEJM paper, titled "CCAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma", describes important similarities between the two cases with both patients having a powerful response to CAR T-cell therapy before developing their secondary blood cancers between five and 16 months after CAR T-cell therapy. Read the paper in full.
CAR T-cell therapy can cure multiple myeloma that has resisted other treatments, and this blood cancer otherwise has a five-year survival rate of 62%.
Patients are already closely monitored in the days and weeks after CAR T-cell therapy to check for a treatable side-effect called cytokine release syndrome, where their immune system responds too strongly.
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