Three studies presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition (December 10, 2017; Atlanta, GA) highlight the emerging role chimeric antigen receptor (CAR) T-cell therapies have in treating certain types of aggressive, refractory blood cancers.
The most recent analysis of ZUMA-1, which combines phase I and II trial data, examined the rate and durability of responses and survival in 108 patients with fast-growing and refractory non-Hodgkin lymphoma (NHL) treated with a single infusion of axicabtagene ciloleucel. Sattva S Neelapu, MD, University of Texas MD Anderson Cancer Center, and colleagues found that after a median follow-up of 15.4 months for these patients, 42% remained in remission and 40% demonstrated no evidence of cancer. This study is the largest study of a CAR-T therapy to date, as it is being conducted at 22 different sites.
Dr Neelapu also explained how this study allows for a few novel revelations of why some patients relapse or do not respond to CAR-T therapy. Researchers found that 33% of patients who relapsed no longer presented with the CD19 protein. They also noticed that more than two-thirds of tumors showed evidence of PD-L1 after relapse. Follow-up studies are currently underway to determine possible strategies to overcoming these issues.
Another interim analysis of a trial (JULIET) involving CAR-T therapy in a type of lymphoma shows improved response and remission rates. Stephen Schuster, MD, Perelman School of Medicine, University of Pennsylvania, and colleagues analyzed results of the open-label, phase II trial – the largest study to examine a CAR-T therapy (tisagenlecleucel) exclusively in patients with diffuse large B-cell lymphoma (DLBCL). A total of 81 patients who had received at least two lines of prior chemotherapy, exhibited disease progression, and had failed to respond or were ineligible for autologous stem cell transplantation were included in the study.
Among the 46 patients with at least 6 months of follow-up, the overall response rate to tisagenlecleucel therapy was 37%, with 30% achieving a complete response and 7% achieving a partial response. Furthermore, among the total patient population, those whose cancer was undetectable at 3 months remained relapse-free at 6 months and beyond. Median durable overall response and overall survival have yet to be reached. Those patients who responded to therapy continue to be followed.
“While we do not completely understand why these remissions are so durable, it is exciting and will change how this disease is treated when conventional therapies fail,” Dr Schuster commented (December 10, 2017). “We are going to be able to offer patients who do not respond to standard therapies a form of therapy that may, after a single treatment, relieve symptoms and save lives.”
A third phase I study—which evaluates an investigational CAR-T therapy targeting BCMA—has also shown encouraging results in patients with previously treated multiple myeloma. Though further research is needed in this disease state, CAR-T therapy looks to be an integral aspect of multiple myeloma care in the near future.
“It is an exciting time. Based on these results and recent FDA approvals in this field, there is reason to be confident that cell therapies, such as CAR-T, may one day be the standard of care for hematologic malignancies as well as solid tumors,” said Renier J Brentjens, MD, PhD, press briefing moderator, medical oncologist and director of cellular therapeutics, Memorial Sloan Kettering Cancer Center (New York, NY).—Zachary Bessette