02.01.22

Cytogenetics Impact on CAR-T cell Therapy Outcomes

Leahy AB, Devine KJ, Li Y, et al. Impact of High-Risk Cytogenetics on Outcomes for Children and Young Adults Receiving CD19-Directed CAR T Cell Therapy. Blood. 2021; (doi: 10.1182/blood.2021012727).

Researchers report that CD19-directed chimeric antigen receptor (CAR) T-cell therapy can enable durable remission for relapsed/refractory relapsed/refractory B-acute lymphoblastic leukemia (ALL) when administered to children and young adults across all cytogenetic categories. For the study, ALL patients were assessed on 5 CD19-directed CAR T-cell (CTL019 or humanized CART19) clinical trials or using commercial tisagenlecleucel from April 2012 to April 2019. Patients were categorized hierarchically based on leukemia cytogenetics, with high-risk defined as KMT2A (MLL) rearrangements, Philadelphia-chromosome (Ph+), Ph-like, hypodiploidy, or TCF3/HLF; favorable as hyperdiploidy or ETV6/RUNX1; and intermediate as iAMP21, IKZF1 deletion, or TCF3/PBX1. Among 231 patients aged 1-29 years, 32% (74) were high-risk, 12% (28) were intermediate, 19% (43) as favorable, and 37% (86) as uninformative. The overall complete remission (CR) rate was 94%. There was no difference in relapse-free survival (RFS), with a two-year RFS for the high-risk group of 63%, nor was there a difference in overall survival (OS), with a 70% two-year rate for the high-risk group. For the 13 patients with KMT2A-rearranged infant ALL, two-year RFS and OS were 67% and 62%, respectively. No elevated relapse risk was seen in multivariable analysis, although more relapses corresponded with myeloid lineage switch and a 3.6-fold higher risk of all-cause death.

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