Hematologic Malignancies: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective: CLL: CAR T-Cell Therapy With Brexucabtagene Autoleucel, By The ASCO Post Staff

摘要

Bijal D. Shah, MD, of the H. Lee Moffitt Cancer Center, discusses phase II results of the ZUMA-3 study, which evaluated brexucabtagene autoleucel (KTE-X19), an anti-CD19 CAR T-cell therapy, in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. A transcript of his interview with The ASCO Post follows. The ZUMA-3 trial is a study of CAR T-cell immunotherapy for adults with relapsed and refractory acute lymphoblastic leukemia. We enrolled patients who had morphologic evidence of disease that is greater than 5% blasts. This could also be accompanied by extramedullary leukemia in the nodal or extranodal areas. Central nervous system (CNS) disease was permitted; however, we limited it to CNS 1 and CNS 2 disease. The Advanced Practitioner Perspective: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia (RR B-cell ALL) have disease that demonstrates resistance to cytotoxic chemotherapy, immunotherapy, and/or allogeneic hematopoietic cell transplantation. For RR B-cell ALL, use of chimeric antigen receptor (CAR) T-cell therapy can be considered if the relapsed disease also expresses a surface protein called CD19. Tisagenlecleucel (Kymriah) is a CAR T-cell therapy with FDA approval to treat patients up to 25 years old in this setting. The therapy works by infusing a patient with genetically engineered cytotoxic T cells that seek and destroy CD19-expressing B-cell ALL cells. The side effect profile of tisagenlecleucel includes but is not limited to potentially life-threatening neurotoxicity. If the patient can be supported through neurotoxicity, typically the effects are completely reversible. Tisagenlecleucel is not used for patients with RR B-cell ALL with CNS involvement due a presumed higher risk of fatal neurotoxicity. Abstract 7002 shares exciting data of brexucabtagene autoleucel (Tecartus), a CD19-directed CAR T-cell therapy, being trialed in older adults between the ages of 40 and 84 years old with RR B-cell ALL and possible CNS involvement. The complete response or complete response with incomplete count recovery rate was approximately 70%. While 25% or 14 total patients developed neurotoxicity, only one died from the same. This significant adverse event must be taken in context, as patients with RR B-cell ALL will likely pass away within days to weeks without treatment. Overall, outcomes were exceptional, as patients experienced a median of 18 months of additional life, which is a remarkable achievement given the aggressive nature of RR B-cell ALL.