The emerging role of anti-PD-1 antibody-based regimen in the treatment of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis

Purpose: Anti-PD-1 antibody (anti-PD-1 mAb) showed favourable outcomes in some patients with relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL). However, the role of anti-PD-1 antibody in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) remains unclear. Here, we evaluated the efficacy and toxicity of anti-PD-1 antibody-based treatment in patients with NK/T-LAHS. Methods The clinical data of 98 NK/T-LAHS patients diagnosed with NK/T-LAHS at Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Guangdong Pharmaceutical University from May 2014 to November 2021were retrospectively analysed. All patients received anti-HLH (HLH-2004 [etoposide, dexamethasone, cyclosporine A] or DEP-based [liposomal doxorubicin, etoposide, methylprednisolone]) regimen and sequential anti-ENKTL chemotherapy (ChT) plus anti-PD-1 antibody or not. Results The overall response rate (ORR) of the anti-PD-1 mAb plus ChT regimens was higher than that of the ChT regimens (73.3% vs. 45.5%, P  = 0.041). The toxicity of the anti-PD-1 mAb plus ChT regimens was tolerable. Except for higher rates of neutropenia, no significant difference in adverse events (AEs) was observed between the two groups. When the best ORR of anti-ENKTL was achieved, the median EBV DNA levels in patients who received anti-PD-1 mAb plus ChT were significantly lower than patients who received ChT only (878 copies/ml vs. 18600 copies/ml, P  = 0.001). With a median follow-up of 26.6 months (range, 0-65.9 months), the median overall survival (mOS) was 3.5 months (95% CI: 2.3–4.7 months). Patients treated with anti-PD-1 mAb plus ChT experienced a longer mOS than those who received ChT only (5.2 months [95% CI: 2.5–7.8 months] vs. 1.5 months [95% CI: 0.5–2.6 months], P  = 0.002). Cox multivariate analysis found that anti-PD-1 mAb was an independent prognostic factor for all NK/T-LAHS patients. Conclusion In conclusion, anti-PD-1 mAb combined with ChT regimens seemed to be associated with prolonged survival in NK/T-LAHS patients and may represent a potentially promising treatment strategy for this population.