CAR T-Cell Therapy Yields Promising Complete Response Rates in Patients With Relapsed/Refractory B-Cell ALL
In a recent study published in Science Translational Medicine, Davila et al found that 88% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who were treated with genetically modified versions of their own immune cells achieved overall complete response. Most patients were able to transition to allogeneic hematopoietic stem cell transplant, the current standard of care.
Adult patients with relapsed B-cell ALL have few treatment options, with only 30% responding to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.
Study Details
In the current study, 16 patients with relapsed B-cell ALL were treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. While the overall complete response rate for all patients was 88%, even those with detectable disease prior to treatment had a complete response rate of 78%, far exceeding the complete response rate of salvage chemotherapy alone.
Seven of the 16 patients (44%) were able to successfully undergo bone marrow transplantation—the standard of care and the only curative option for patients with B-cell ALL—following treatment. Three patients were ineligible due to failure to achieve a complete response, three were ineligible due to preexisting medical conditions, two declined, and one is still being evaluated for a potential bone marrow transplant. Historically, only 5% of patients with relapsed B-cell ALL have been able to transition to bone marrow transplantation.
The study also provides guidelines for managing side effects of cell therapy, which can include severe flu-like symptoms such as fever, muscle pain, low blood pressure, and difficulty breathing, referred to as cytokine release syndrome. The researchers developed diagnostic criteria and a laboratory test that can identify which patients are at greater risk for developing this syndrome.
“These … results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies,” said study author Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center. “Our initial findings have held up in a larger cohort of patients, and we are … looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”
Additional studies to determine whether cell therapy can be applied to other types of cancer are already underway, and studies to test whether patients with B-cell ALL would benefit from receiving targeted immunotherapy as front-line treatment are being planned.
Dr. Sadelain and Renier Brentjens, MD, PhD, of Memorial Sloan Kettering Cancer Center, are the corresponding authors for the Science Translational Medicine article.
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®.
