Chimeric antigen receptor (CAR) natural killer (NK) cell therapy that targets the CD19 antigen has yielded promising results for patients with a range of B-cell malignancies.
Researchers from The University of Texas MD Anderson Cancer Center, USA, said they were pleased with the results of a phase I/II trial of 37 patients with relapsed or refractory B-cell malignancies who were treated with cord blood-derived CAR NK cell therapy targeting CD19.
Writing in Nature Medicine, they said there was an overall response (OR) rate of 48.6% at 100 days post treatment, with one-year progression-free survival (PFS) and overall survival (OS) rates of 32% and 68%, respectively.
They also reported an ‘excellent’ safety profile, with no cases of severe cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host disease.
The research team highlighted the importance of the selection criteria for allogeneic cord blood donors in CAR NK cell manufacturing.
Cord blood units that were cryopreserved within 24 hours of collection and those with a low nucleated red blood cell content were associated with significantly better outcomes.
CAR NK cells generated from these ‘optimal’ units resulted in a one-year PFS rate of 69% and an OS rate of 94%, compared to 5% and 48%, respectively, from those ‘suboptimal’ units with higher nucleated red blood cell content or longer collection-to-cryopreservation times.
Senior author Dr Katy Rezvani, professor of stem cell transplantation and cellular therapy, said: “The responses observed in these patients are very encouraging as we continue to evaluate the long-term efficacy of CAR NK cells in the treatment of these malignancies.
“In order to have a successful allogeneic cell therapy, it is also critical that we identify the characteristics of an optimal allogeneic donor for CAR NK manufacturing. We were able to identify two key factors associated with cord blood units most likely to yield a positive clinical response and discerned the biologic mechanisms underlying this phenomenon.”
The study also noted encouraging response rates across different types of B-cell malignancies. The OR rate at 30 days post treatment was 100% for patients with low-grade non-Hodgkin’s lymphoma (NHL), 67% for those with chronic lymphocytic leukaemia (CLL) without transformation and 41% in patients with diffuse large B-cell lymphoma (DLBCL).
Researchers also observed durable responses with CAR NK cell treatment. One year after treatment, complete responses were seen in 83% of patients with low grade-NHL, 50% of patients with CLL and 29% of patients with DLBCL.
Individuals with a response at 30 days post treatment were significantly more likely to have PFS at one-year after treatment.
These results build on previous data from this trial, published in the New England Journal of Medicine, which showed a single infusion of CAR NK cells achieved remission in 73% of a smaller cohort of patients with B-cell malignancies.
Dr Rezvahni said: “Our study stresses the importance of identifying donor-specific predictors of response after allogeneic cell therapy, especially since one donor may be used to treat hundreds of patients. CAR NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use.
“This could potentially increase patient access to these cell therapies, reduce treatment time and lower cost of therapy.”
Source:
Marin D, Li Y, Basar R, Rafei H, Daher M, Dou J, Mohanty V, Dede M, Nieto Y, Uprety N, Acharya S, Liu E, Wilson J, Banerjee P, Macapinlac HA, Ganesh C, Thall PF, Bassett R, Ammari M, Rao S, Cao K, Shanley M, Kaplan M, Hosing C, Kebriaei P, Nastoupil LJ, Flowers CR, Moseley SM, Lin P, Ang S, Popat UR, Qazilbash MH, Champlin RE, Chen K, Shpall EJ, Rezvani K. (2024) “Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial.” Nature Medicine, doi: 10.1038/s41591-023-02785-8.
Link: https://www.nature.com/articles/s41591-023-02785-8
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