Early Findings Show Promise of CAR NK-Cell Therapy in Leukemia, Lymphoma

February 8, 2020

Patients with either relapsed or refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with CAR NK cells had a response without the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease.

Early results from a phase I/II trial, published in The New England Journal of Medicine, found that a majority of patients with either relapsed or refractory non-Hodgkin’s lymphoma (NHL) or chronic lymphocytic leukemia (CLL) treated with CAR NK cells had a response without the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease.1

Additionally, there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline; however, the maximum tolerated dose was not reached.

“We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need,” corresponding author Katy Rezvani, MD, PhD, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center, said in a press release.2

In this study cohort of 11 patients with relapsed or refractory CD-19 positive cancers, participants were given a single dose of cord blood-derived CD19 CAR NK cells at 1 of 3 dose levels. Five of the patients had CLL and the remaining 6 had NHL. All of the patients were treated with a minimum of 3 and a maximum of 11 lines of prior therapy. The first 9 participants treated were given CD19 CAR NK cells that were partially matched according to the individual’s HLA type, but protocol allowed the last 2 patients to be treated with no HLA matching. 

Eight (73%) of the participants had a response, and of those, 7 (4 with NHL and 3 with CLL) had a complete remission, while 1 had remission of the Richter’s transformation component, but had persistent CLL. The responses were rapid and observed within 30 days after infusion at all dose levels. The infused CAR NK cells expanded and persisted at low levels for at least 12 months.

According to the researchers, a proportion of patients treated with anti-CD19 CAR T cells have a subsequent relapse, with a 1-year progression-free survival of approximately 30% observed among patients with CLL and 45% seen among those with NHL.

“In view of these outcomes, our study allowed for remission consolidation therapy with an immunomodulatory agent, anticancer drug, or hematopoietic stem-cell transplantation at the discretion of the treating physician,” the authors wrote. “However, the use of post-remission therapy in this study limits our assessment of the durability of response after CAR NK therapy.”

Notably, researchers did observe high-grade transient myelotoxicity in the cohort, of which they attributed to the lymphodepleting chemotherapy. However, they were unable to assess whether the CAR NK cells contributed to the myelotoxicity. 

Side effects experienced by the patients were primarily related to the conditioning chemotherapy given before cell infusion and were resolved within 1 to 2 weeks, according to Rezvani. Additionally, no patient required admission to an intensive care unit for management of treatment side effects. 

“Due to the nature of the therapy, we’ve actually been able to administer it in an outpatient setting,” Rezvani said. “We look forward to building upon these results in larger multi-center trials as we work with Takeda to make this therapy available more broadly.”

References:

1. Liu E, Marin D, Banerjee P, et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. The New England Journal of Medicine. doi:10.1056/NEJMoa1910607.

2. CD19 CAR NK-cell therapy achieves 73% response rate in patients with leukemia and lymphoma [news release]. Houston, Texas. Published February 5, 2020. app.bronto.com/public/viewmessage/html/6781/hemm7h92mwb6849npf2js0r4mhnrl/0bd003eb00000000000000000000000df096. Accessed February 6, 2020.