Piers Blombery, MBBS, PhD, on Investigating CAR+ T-Cell Lymphoma After Cilta-Cel

“It looks there’s a contribution of possibly where the CAR's inserted, into a...premalignantT-cell, in a patient with a potential germline mutation predisposition to developing this malignancy and that appears together to have caused a CAR T uncontrolled lymphoproliferation. There’s always a lot of work to be done and a lot of work we’re doing at the moment to further understand the contribution of all 3 parts but that's where we are at the moment.”

New research out of the Peter MacCallum Cancer Centre in Australia has reported on a case study of the first described case of chimeric antigen receptor (CAR)+ T-cell lymphoma due to lentiviral transduction in a patient with multiple myeloma treated with ciltacabtagene ciloleucel (Carvykti; Janssen, Legend Biotech) in the phase 3 CARTITUDE-4 study (NCT04181827). The research was described in an abstract accepted to the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California, as an online publication.

CGTLive spoke with the abstract’s senior author, Piers Blombery, MBBS, PhD, associate professor, Peter MacCallum Cancer Centre, and head, Wilson Centre for Blood Cancer Genomics, to learn more about the case of CAR+ lymphoma. He described possibly characteristics of the patient that may have lead to the oncogenesis, including a dysregulated PBX2 gene, TET2 clonal hematopoiesis, and a JAK3-activating allele germline mutation, although these are educated guesses. As these findings are based only off of one patient, Blombery stressed that further research is necessary to make definitive conclusions about the case, and that his team is continuing to investigate it.

REFERENCE

Harrison SJ. Nguyen T, Rahman M, et al. CAR+ T-Cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma. Blood (2023): 142; 1. 6939. doi: 10.1182/blood-2023-178806