CAR T-Cell Therapy Effective for Children With ALL, Updated Study Results Show

Final updated results of the pivotal phase 2 study that led to last year’s FDA approval of the first chimeric antigen receptor (CAR) T-cell therapy were published Wednesday in the New England Journal of Medicine. A novel way to treat cancer, CAR T-cell therapy genetically reprograms a patient’s own white blood cells to attack tumor cells.

In August 2017, Novartis gained approval for tisagenlecleucel (Kymriah) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in certain pediatric and young adult patients.

Results of the the study release Wednesday reports on 75 evaluable patients between 3 to 21 years of age with relapsed or treatment refractory B-cell ALL. Of these, 61% had relapsed after allogeneic hematopoietic stem cell transplantation, an intensive therapy whose failure leaves few options.

In the interim analysis, which included 50 patients, the primary endpoint was met, with an overall remission rate of 82% (95% CI, 69 to 91; P <.001).

In this updated analysis involving 75 patients who received a tisagenlecleucel infusion and had at least 3 months of follow-up, the overall remission rate was 81% (95% CI, 71 to 89); 45 patients (60%) had complete remission, and 16 (21%) had complete remission with incomplete hematologic recovery.

All patients who had a best overall response of complete remission with or without complete hematologic recovery were negative for minimal residual disease; 95% (58 of 61) of these patients were negative by day 28. In an intention-to-treat analysis of the full enrolled population (92 patients), which included patients who discontinued participation in the study before tisagenlecleucel infusion, the overall remission rate was 66% (95% CI, 56 to 76).

For comparison, the paper cites clorafabine, a pediatric chemotherapy treatment for relapsed or refractory ALL; it produced a response rate of 20% with a median overall survival time of 13 weeks.

Substantial side effects are associated with CAR T; grade 3 or 4 adverse events that may have been related to the therapy occurred in 73% of patients. The most significant side effects included cytokine release syndrome, often requiring admission to an intensive care unit, and neurological events in 40% of patients. The study's lead author, Shannon L. Maude, MD, PhD, of The Children's Hospital of Philadelphia, discussed those side effects with The American Journal of Managed Care^® at the American Society of Hematology Annual Meeting and Exposition in 2017.

"The main side effects of this therapy are within the first 28 days," she said. "But there’s lots of monitoring and potential for long-term side effects, as well."

CAR T-cell therapy was recently named the Advance of the Year by the American Society of Clinical Oncology.

Reference

Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia. N Engl J Med 2018; (378):439-448. DOI: 10.1056/NEJMoa1709866