CAR-T Therapy, HSCT May Improve ALL Survival Without Increased Risk of Toxicity
Chimeric antigen receptor (CAR) T-cell therapy may compliment hematopoietic stem cell transplantation (HSCT) for improving survival in acute lymphoblastic leukemia (ALL) without increasing the risk of severe graft-versus-host disease (GVHD), according to research presented at the 2018 BMT Tandem Meetings (February 21-25; Salt Lake City, UT).
While CAR-T therapy has demonstrated promise in the treatment of hematologic malignancies, some patients do not benefit from durable responses. HSCT has the potential to be curative for patients with relapsed or refractory ALL, especially for those in minimal residual disease-negative remission.
Haneen Shalabi, DO, Pediatric Oncology Branch, National Cancer Institute, and colleagues conducted a study to assesses the depth of remission, CAR-T therapy persistence, and post-transplant toxicity in an effort to further understand the role of CAR-T therapy in the peri-HSCT setting of ALL. Included in the study were children and young adults with relapsed or refractory CD19-positive or CD22-positive ALL who were treated in a phase I trial of anti-CD19 CAR-T therapy (n = 55) or anti-CD22 CAR-T therapy (n = 36).
Researchers noted that 54 patients achieved a complete response, 45 of whom achieved minimal residual disease negativity by flow cytometry and 25 of whom received stem cell transplant. Among the 20 remaining patients who did not receive stem cell transplant, 19 had prior HSCT and 16 had relapsed after CAR-T infusion.
Researchers utilized a competing-risk analysis to compare risk for relapse vs risk for transplant-related mortality. Results showed a 24-month cumulative incidence of post-HSCT relapse was 13% among all patients who underwent HSCT compared with 11.3% among patients undergoing their first HSCT.
Additionally, 10 patients (40%) developed acute GVHD, 12% of whom had grade 3/4 disease. These rates were comparable to the expected rates of GVHD post-HSCT, researchers noted.
Results of the study led researchers to conclude that CAR-T therapy may serve as a safe and effective treatment option prior to transplantation for ALL. They further noted that CAR persistence may not impact post-HSCT outcomes, and shorter-acting CARs may be preferred when HSCT is an available option.
“All [CAR-T therapies] are created differently,” Shalabi said in her presentation. “With shorter-acting CAR T-cells, the persistence is not there. In this high-risk patient population, some of whom have never achieved remission, taking them to transplant would be the optimal treatment after CAR-T.”—Zachary Bessette