Kim, Seok Jin Lim, Jing Quan Yoon, Sang Eun Yang, Deok-Hwan Lee, Ji Hyun Oh, Sung Yong Choi, Yoon Seok Jeong, Seong Hyun Kim, Min Kyoung Lim, Sung Nam Cho, Junhun Park, Bon Ryu, Kyung Ju Choi, Seung hyun Park, Yoon Lim, Kerry May Huifen Taib, Nur Ayuni Binte Muhammad Ong, Choon Kiat Lim, Soon Thye Kim, Won Seog 2025-08-20T08:38:59Z 2025-08-20T08:38:59Z 2025-08-20 2025-07 0006-4971 https://pubs.kist.re.kr/handle/201004/153012 This study aimed to assess the efficacy and safety of combining cemiplimab, an anti–programmed cell death protein 1 (PD-1) antibody, with isatuximab, an anti-CD38 antibody, in relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL). The hypothesis was that CD38 blockade could enhance the antitumor activity of PD-1 inhibitors. Eligible patients received cemiplimab (250 mg on days 1 and 15) and isatuximab (10 mg/kg on days 2 and 16) IV every 4 weeks for 6 cycles. Responders then received cemiplimab (350 mg) and isatuximab (10 mg/kg) every 3 weeks for up to 24 months. The primary end point was the complete response (CR) rate based on the best response. Of 37 patients enrolled, the CR rate was 51% (19/37), exceeding the primary end point of 40%, and the objective response rate was 65% (24/37). After a median follow-up of 30.2 months (95% confidence interval [CI], 25.6-34.8 months), the median progression-free survival was 9.5 months (95% CI, 1.4-17.6 months), whereas the median overall survival had not yet been reached. Patients achieving CR received a median of 28 cycles (range, 4-33 cycles), and the median duration of response for responders (n = 24) was 29.4 months (95% CI, 15.4-43.4 months). Structural variations disrupting the 3’-untranslated region of PD-L1 and high programmed death ligand 1 (PD-L1) expression were observed in responders. Most adverse events were mild (grade 1-2), with grade ≥3 events (32%) and no treatment-related deaths. The combination of isatuximab and cemiplimab demonstrated sustained antitumor activity and a manageable safety profile in R/R ENKTL. This phase 2 trial is registered at www.clinicaltrials.gov as number NCT04763616. English American Society of Hematology Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma Article 10.1182/blood.2024027109 1 Blood, v.146, no.2, pp.155 - 166 Blood 146 2 155 166 N scie scopus 001533972400010 2-s2.0-105001984003 Hematology Hematology Article PHASE-II NASAL MULTICENTER PEMBROLIZUMAB PREDICTS POOR-PROGNOSIS PERIPHERAL T-CELL