CAR-T Cell Success in Late-Stage ALL

A small study in 30 patients with advanced B-cell acute lymphoblastic leukemia (ALL) has further strengthened the faith in the potential of chimeric antigen receptor (CAR)-T cell therapy.

Thirty patients with B-cell ALL participated in the study, which was conducted at the Fred Hutchison Cancer Research Center. CAR-T cells are genetically modified T cells that have been collected from patients and made to overexpress the CD19-specific CAR protein, which allows the cells to target and kill cancer cells that express CD19. Only adult patients with advanced disease were enrolled in the trial that was designed to evaluate the safety of administering these genetically-modified cells.

The procedure involves extracting the patients’ T cells, overexpressing the CAR protein using a viral vector, expanding the modified cells in vitro in the laboratory, and infusing them back into the patient following chemotherapy, about 2 weeks following their extraction—lymphodepletion chemotherapy followed by leukapheresis. All 30 patients, the authors report, had previously received a median of 3 prior intensive chemotherapy regimens (range 1 to 11), and 11 patients had relapsed at a median of 7 months (range 1 to 28 months) after prior allogeneic hematopoietic stem cell transplant.

The authors report that 27 of 29 patients who were evaluated a few weeks after the infusion did not have any detectable levels of cancer in their bone marrow. Additionally, one of the 2 patients who did not present with complete remission received a higher dose of the cells, resulting in a complete remission.

However, neurotoxicity and severe cytokine release syndrome (commonly called a cytokine storm) were a common toxicity associated with this treatment. The authors recommend risk-stratified CAR-T cell dosing to reduce this toxicity. Additionally, including the antimetabolite fludarabine to the lymhodepletion regimen improved CAR-T cell persistence and disease-free survival according to the authors.

The study authors are enthused by these results. “Patients who come onto the trial have really limited options for treatment. They have refractory, acute leukemia. So the fact that we're getting so many into remission is giving these people a way forward,” said first author Cameron Turtle, MD,in a statement. “This is just the beginning. It sounds fantastic to say that we get over 90 percent remissions, but there's so much more work to do make sure they're durable remissions, to work out who's going to benefit the most, and extend this work to other diseases,” he added.

Reference

Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients [published online April 25, 2016]. J Clin Invest. pii:85309. doi:10.1172/JCI85309.