Bachanova V, et al. - In this study, a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5–3.27 × 10⁷ NK cells/kg) with rituximab and IL-2 was reported. For advanced NHL, findings supported the development of donor NK cellular therapies as a strategy to overcome chemoresistance.

• Without graft-versus-host disease, cytokine release syndrome, or neurotoxicity the therapy was tolerated.
• Researchers recognoized 14 evaluable patients.
• Four of these indicated objective responses (29%; 95% CI 12–55%) at 2 months: 2 had complete response lasting 3 and 9 months.
• They noticed persistence of circulating donor NK cells for at least 7 days after infusion at the level 0.6–16 donor NK cells/μl or 0.35–90% of total CD56 cells.
• Responding patients compared to non-responding patients indicated lower levels of circulating host-derived Tregs (17 ± 4 vs 307 ± 152 cells/μL; p=0.008) and myeloid-derived suppressor cells at baseline (6.6 ± 1.4% vs 13.0 ± 2.7%; p=0.06).
• They noticed a correlation of lower circulating Tregs with low serum levels of IL-10 (R₂ = 0.64; p < 0.003; n = 11), suggestive of less immunosuppressive milieu.
• In this study, low expression of PD-1 on recipient T cells before therapy seemed to have association with response.
• In responders compared to non-responding patients, endogenous IL-15 levels were higher at the day of NK cell infusion (mean ± SEM: 30 ± 4; n = 4 vs 19.0 ± 4.0 pg/ml; n = 8; p=0.02) and correlated with day 14 NK cytotoxicity as measured by expression of CD107a (R₂ = 0.74; p = 0.0009; n = 12).