ASH 2016: New CAR T-Cell Therapy Holds Promise for Children and Young Adults With Hard-to-Treat ALL in Phase I Trial
Children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor (CAR) T-cell therapy targeting CD22, a protein found on the surface of leukemic cells, appear to mount a clinical response and, in some cases, achieve remission. Researchers from the Pediatric Oncology Branch of the National Cancer Institute of the National Institutes of Health genetically altered patients’ own T cells to track down and kill cancer cells expressing CD22. The study—the first to evaluate CAR targeting CD22 in humans—also gives a first glimpse into how patients who already received CAR-T therapy directed at a different antigen, CD19, might fare when given a second immunotherapy. It was presented by Shah et al at the 58th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 650).
Study Findings
Data were presented for 16 patients who received the new anti–CD22 therapy. One of the six patients treated at a lower dose initially set by the U.S. Food and Drug Administration and other agencies attained remission. The majority—8 of 10—participants treated at a higher dose level (a dose comparable to that used by current CD19 CAR programs) attained a complete remission without evidence of residual disease after 1 month of their infusion. There have since been relapses among six out of nine patients who achieved remission, the majority of which are due to drops in CD22 expression on the cells, which has similarly been observed with CD19 CAR therapy. So far, one patient remains in remission beyond 1 year.
“We’ve been able to show that you can give a second CAR therapy that is directed against a different antigen and have it be safe and effective,” said study author Terry J. Fry, MD, of the Center for Cancer Research at the National Cancer Institute.
Dr. Fry said this adds to the notion that a single antigen-directed CAR immunotherapy probably won’t be sufficient for long-term durable remissions in many patients, and points to the potential for targeting multiple cancer-related proteins (also called bispecific targeting).
Further Study Information
Participants in this phase I trial had relapsed or treatment-resistant ALL, and were either CAR-naive or previously treated with anti–CD19 CAR T cells and/or blinatumomab therapy. Some who became resistant to CD19 CAR did so due to loss of CD19. The patients, ranging in age from 7 to 22 years old, all had CD22–positive ALL and had previously undergone at least one allogeneic stem cell transplant. A majority of participants (11 out of 16) had relapsed after receiving anti–CD19 CAR T-cell therapy before entering the trial. Researchers collected T cells from eligible patients and modified them to recognize and bind to CD22. Patients then received an infusion of their own modified cells and were evaluated for response and adverse effects after an average of 28 days.
The primary adverse event was cytokine release syndrome, a common, potentially dangerous reaction to this type of infusion, which Dr. Fry reports was mild in all cases—fever and low blood pressure were the main symptoms. There was one death due to sepsis that occurred after resolution of cytokine release syndrome.
While the trial is continuing to accrue patients, these early results raise new questions about how anti–CD22 CAR therapy might best be used; for example, if it is better to wait for relapse after initial CAR therapy or preempt it by cotreating it. Dr. Fry and his team plan to further investigate the combined use of anti–CD19 and CD22 CAR targeting approaches with the hypothesis that this will increase the likelihood of sustained remission.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
