Expansion of natural killer (NK) cells with interleukin (IL)-15 and nicotinamide for adoptive cell transfer for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) resulted in a high response rate in a small phase 1 trial.
NK cells incubated with nicotinamide also demonstrated makers of enhanced stability and showed greater persistence.
A first-in-human, phase 1, dose-escalating study (ClinicalTrials.gov identifier: NCT03019666), which was published in the Science Translational Medicine, treated 39 patients with advanced NHL or MM with NK cellular therapy. NK cells were expanded in the presence of nicotinamide, also known as GDA-201, and IL-15 prior to adoptive transfer. Patients with NHL or MM were treated with lymphodepleting chemotherapy plus 3 doses of rituximab or elotuzumab, respectively, followed by IL-2 plus GDA-201.
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Among 19 evaluable patients with NHL, the overall response rate was 74%, with 57% of patients achieving a complete response, and the median duration of response was 16 months. Within 28 days, a clinical response was observed among all patients after GDA-201.
The 1- and 2-year progression-free survival was 50% and 35%, respectively. There were no reports of cytokine release syndrome or neurotoxicity. Thrombocytopenia, febrile neutropenia, and anemia were the most common grade 3-4 adverse events.
The authors also evaluated the expansion of NK cells with IL-15 and nicotinamide in vitro. Compared with cells cultured with only IL-15, the addition of nicotinamide resulted in induction of CD62L, which is lymphocyte adhesion molecule involved in lymph node homing.
The addition of nicotinamide impaired proteasomal degradation of FOXO1. Increased levels of this transcription factor are associated with higher levels of CD62L.
Incubation with nicotinamide also increased glucose flux, showed protection against oxidative stress, promoted cytotoxicity, and increased inflammatory cytokine production. NK cell expansion in the presence of nicotinamide and IL-15 improved persistence after adoptive cell transfer in xenograft animal models.
“The safety and efficacy of GDA-201 in this study support further development as a cancer therapy,” the authors concluded in their report. A phase 1 study of GDA-201 is ongoing.
Disclosures: The clinical trial was supported by Gamida Cell Ltd. Please see the original reference for a full list of disclosures.
Reference
Cichocki F, Zhang B, Wu C-Y, et al. Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma. Sci Transl Med. 2023;15:eade3341. doi: 10.1126/scitranslmed.ade3341
