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ASH 2017: ZUMA-1: Responses to CAR T-Cell Therapy Still Strong After 1 Year in Patients With Refractory NHL

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Key Points

  • More than 1 year after a single infusion of axicabtagene ciloleucel, 42% of patients remain in remission and 40% of patients exhibit no evidence of cancer.
  • 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.
  • 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. More than two-thirds of tumors showed evidence of PD-L1, likely helping the cancer cells survive by inhibiting the function of the infused T cells.

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 called axicabtagene ciloleucel that targets the CD-19 protein frequently found on cancerous lymphoma cells, reported Neelapu et al at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 578).

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 axicabtagene ciloleucel, 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.”

More on ZUMA-1

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 axicabtagene ciloleucel 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 axicabtagene ciloleucel 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 programmed programmed cell death ligand 1 (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.

A randomized trial to compare the efficacy of this therapy with second-line standard of care, which includes autologous stem cell transplantation for relapse after first-line therapy, is planned in patients with aggressive B-cell NHL.

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®.


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