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 data was presented in a press conference at the 2017 ASH annual meeting. 

For more information watch our interview with Dr Sattva Neelapu.

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 one year after a single infusion of axi-cel, 42 percent of patients remain in remission and 40 percent 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 percent — 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 two 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 six 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 analysing tumour 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 tumours 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.

There are roughly 72,000 new cases of NHL in the U.S. each year.

NHL starts in white blood cells called lymphocytes, which are part of the immune system.

There are two main types of lymphocytes — B-cells and T-cells — whose role is to help the body fight infection.

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.

Source: ASH 2017