For people with certain types of aggressive, refractory blood cancers, treatment options are woefully limited. But a study being presented today at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta spotlights the emerging role played by chimeric antigen receptor (CAR) T-cell therapies in helping individuals mount a clinical response and, in some cases, achieve durable remission.

These therapies are designed by harvesting a patient’s own T cells (the immune system’s primary cancer-killing cells), reengineering them to target specific proteins on the surface of leukemia and lymphoma cells, and reintroducing the modified T cells back into the patient’s immune system.

“It is encouraging that the data continue to be so strong and suggest that CAR-T therapies for B-cell malignancies are here to stay,” said press briefing moderator, Renier J. Brentjens, MD, PhD, medical oncologist and director of cellular therapeutics at Memorial Sloan Kettering Cancer Center. “There is still a lot we need to learn about toxicities—for example, how to manage cytokine release syndrome (CRS), a common, potentially dangerous reaction to this type of infusion.”

In two separate, longer-term follow-up analyses (of the ZUMA-1 and JULIET trials), researchers found that initial responses were sustained over time in patients who received genetically modified T cells designed to target the CD-19 protein, which is frequently expressed on malignant lymphoma cells. A third, Phase I study—one of the largest to evaluate a CAR therapy targeting BCMA, a marker present on the vast majority of multiple myeloma tumor cells—showed encouraging early results in patients with heavily pre-treated multiple myeloma.

“It’s 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 Dr. Brentjens.

Among 108 patients with fast-growing and refractory aggressive non-Hodgkin lymphoma (NHL), more than half were still alive at least a year after receiving a single infusion of a CAR T-cell therapy, axicabtagene ciloleucel (axi-cel), that targets the CD-19 protein frequently found on cancerous lymphoma cells, researchers reported. This latest analysis of ZUMA-1, which combines Phase I and II trial data, assessed the rate and durability of responses and survival among these patients after a median follow-up of 15.4 months. More than 1 year after a single infusion of axi-cel, 42% of patients remain in remission and 40% of patients exhibit no evidence of cancer.

“Long-term follow-up of ZUMA-1 confirms that these responses can be durable, and the ongoing responses at 24 months suggest that late relapses are uncommon. Patients who are in remission at 6 months tend to stay in remission,” said lead study author Sattva S. Neelapu, MD, professor at The University of Texas MD Anderson Cancer Center. “With existing therapy, the median survival for people with this disease is only 6 months. Here, we see more than half of patients—59%—are still alive over a year after treatment.”

The study, which is being conducted at 22 sites, is the largest study of a CAR T-cell therapy’s efficacy to date, according to researchers. Dr. Neelapu explains that the durability findings are also consistent with observations from earlier, single-institution trials of axi-cel in this patient population. In terms of safety, no new deaths related to the therapy occurred. Early in the study, four patients died within 2 months of treatment—two attributable to the CAR T-cell therapy and the other two to unrelated adverse side effects that are typical of disease progression. In the pivotal portion of ZUMA-1, common adverse events consisted of CRS, neurologic toxicities, neutropenia, anemia, and thrombocytopenia. Ten patients experienced a serious adverse event 6 months after the primary analysis, including infections in eight patients. No new-onset CRS or neurologic events related to axi-cel were observed in the updated analysis.

The study also provides some of the first clues as to why some patients relapse or do not respond to CAR T-cell therapy. After analyzing tumor tissue from before and after treatment in patients who relapsed, the researchers found that in a third of patients the CD19 protein was no longer present on cancer cells. Secondly, more than two-thirds of tumors showed evidence of another protein, PD-L1, likely helping the cancer cells survive by inhibiting the function of the infused T cells. Follow-up studies are now underway to identify possible approaches to overcoming these problems.