Mount Sinai Team Successfully Treats T-Cell Lymphoma Secondary to CAR T-Cell Therapy

A team of researchers from the Icahn School of Medicine at Mount Sinai in New York City successfully treated a patient who developed a rare secondary T-cell lymphoma after receiving chimeric antigen receptor (CAR) T-cell treatment; the team turned to genomic, phenotypic and functional profiling to identify an effective treatment strategy. The case study was reported in The New England Journal of Medicine.

“As more patients receive CAR T-cell therapy, awareness of secondary cancers is essential,” the team wrote.

The patient, a 51-year-old man, was treated for multiple myeloma using the CAR T-cell therapy ciltacabtagene autoleucel (Carvykti, Johnson & Johnson) which targets B-cell maturation antigen (BCMA). Six months after treatment, the patient developed erythematous lesions on the face and lymphocytosis. PET scan revealed hypermetabolic lesions in the nose and cheeks.

Genomic testing of skin biopsies and bone marrow revealed that the lymphoma cells contained the genetic sequence from the CAR T-cell therapy and had evolved from one of the infused CAR T cells — a vanishingly rare complication.

Additional sequencing revealed high expression of CCR4, confirming the diagnosis of cutaneous T cell lymphoma. High CCR4 expression identified a treatment target. Based on this finding, the team selected mogamulizumab for treatment.

The team also performed transcriptome profiling — a technique to determine which genes are “turned on” — which allowed them to identify cancer pathways that they could target with treatment. Once they had the transcriptome profile, they performed an ex vivo screen of 166 drugs, which identified the tumor as being sensitive to anthracyclines. As a result, liposomal doxorubicin and gemcitabine were added to mogamulizumab as part of the treatment regimen.

The patient achieved complete remission and remained cancer-free at the 10-month follow-up.

The team suggested that future work should “dissect the interplay of vector-integration, acquired genetic and epigenetic lesions, cytokine-driven proliferation and serial infections in driving T-cell transformation and lymphomagenesis.”