‘Off-the-shelf’ cell therapy shows ‘very encouraging’ results for B-cell malignancies
Key takeaways:
- Approximately one-half of study participants responded to CAR-NK cell therapy.
- Researchers identified multiple cell donor-related characteristics leading to improved treatment outcomes.
Nearly one-half of adults with relapsed or refractory CD19-positive B-cell malignancies responded to treatment with a novel cord blood-derived natural killer cell therapy expressing a chimeric antigen receptor, study results showed.
Results from the phase 1/phase 2 trial — published in Nature Medicine — also suggest a durable response for patients who respond to therapy and no major treatment-related toxicities, according to researchers.
“The responses observed in these patients are very encouraging as we continue to evaluate the long-term efficacy of CAR-[natural killer (NK)] cells in the treatment of these malignancies,” 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.
“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,” she added. “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.”
Background and methodology
Researchers conducted the trial to determine the saftey and efficacy of CAR-NK cells in patients with CD19-positive B-cell malignancies. The study included 37 patients who received cord blood-derived NK cells expressing an CD19-directed CAR and interleukin-15.
Safety and efficacy — defined as day 30 overall response (OR) rate — served as the study’s primary outcome measurements, with secondary outcomes including day 100 OR rate, PFS, OS and anti-CD19 CAR and interleukin-15 cell persistence.
Results, next steps
Researchers reported identical day 30 and day 100 OR rates of 48.6%.
An analysis of survival outcomes showed a 1-year OS rate of 68% and 1-year PFS rate of 32%.
Patients who achieved an OR had higher levels and longer persistence of CAR-NK cells; researchers also noted that receiving CAR-NK cells from a cord blood unit with nucleated red blood cells 8 × 107 and a collection-to-cryopreservation time 24 hours as the most significant predictors for superior outcomes.
NK cells from optimal cord blood units appeared to be highly functional and enriched in effector-related genes, according to researchers. Meanwhile, NK cells from suboptimal cord blood units had upregulation of inflammation, hypoxia and cellular stress programs.
Study investigators noted a lack of major toxicities typically associated with cellular therapy and transplantation (eg, cytokine release syndrome, neurotoxicity, graft-versus-host disease) among study participants.
According to researchers, the results provide oncologists with new insight into the cell biology of CAR-NK and highlight the significance of donor selection for allogenic cell therapies.
“Our study stresses the importance of identifying donor-specific predictors of response after allogenic cell therapy, especially since one donor may be used to treat hundreds of patients,” Rezvani said in the release.
“CAR-NK cells have the potential to be manufactured in advance and stored for off-the-shelf immediate use,” she added. “This could potentially increase patient access to these cell therapies, reduce treatment time and lower cost of therapy,” she added.
References:
- CD19-targeted CAR NK cell therapy achieves promising one-year results in patients with B-cell malignancies (press release). Available at: https://www.mdanderson.org/newsroom/cd19-targeted-car-nk-cell-therapy-achieves-promising-one-year-results-patients-B-cell-malignancies.h00-159694389.html. Published Jan. 17, 2024. Accessed March 5, 2024.
- Marin D, et al. Nat Med. 2024;doi:10.1038/s41591-023-02785-8.
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