Isatuximab and Cemiplimab in Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Multi-Center, Open-Labeled Phase II Study (CISL2102/ICING study)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.301-301
• Main Authors: Kim, Seok Jin, Yoon, Sang Eun, Yang, Deok-Hwan, Oh, Sung Yong, Choi, Yoon Seok, Jeong, Seong Hyun, Kim, Min Kyoung, Lim, Sung-Nam, Cho, Junhun, Kim, Won Seog
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-174476

Introduction Extranodal NK/T-cell lymphoma (ENKTL), an Epstein-Barr virus (EBV) associated lymphoid malignancy is a rare but aggressive non-Hodgkin lymphoma (NHL). The prognoses of patients with relapsed or refractory (R/R) ENKTL are still poor because there is limited treatment option for R/R ENKTL. The expression of PD-L1 (Programmed Death Ligand-1) is common in ENKTL because EBV could induce the PD-L1 expression. Thus, PD1 and PD-L1 inhibitors have been tried as salvage treatments, but their single-agent activities in previous studies were not satisfactory. CD38 has been considered as another potential therapeutic target in ENKTL because tumor cells of ENKTL could express CD38. CD38 expression was also reported to be related with the resistance to PD1 inhibitors. Thus, we conducted a phase II study with the combination of cemiplimab (PD1 inhibitor) and isatuximab (monoclonal anti-CD38 antibody) in patients with R/R ENKTL. Methods We aimed to analyze the efficacy of isatuximab (anti-CD38 monoclonal antibody) and cemiplimab (anti-PD1 monoclonal antibody) in patients with R/R ENKTL. Patients eligible for this study had relapsed or refractory disease at least one line of treatment. The induction treatment consisted of cemiplimab 250mg (day 1 and 15) and isatuximab 10mg/kg (day 2 and 16) intravenous administration every 4 weeks for 6 cycles. After that, responders received cemiplimab 250mg and isatuximab 10mg/kg once every 3 weeks up to 24 months or until progression, death, or study withdrawal. The primary end point was complete response (CR) rate and secondary end points were objective response rate (ORR) consisting of CR and partial response (PR), progression-free survival (PFS), and safety. The target CR rate was designated as 40% (P1). Considering 20% (P0) of CR rate after conventional salvage therapies and 10% of drop-out rate, 37 patients were planned to be enrolled. Results Between June 2021 and May 2023, we enrolled 37 patients. At enrollment, 29 (78%) patients had stage IV disease and 26 (70%) belonged to the high-risk of prognostic index of NK lymphoma (PINK-E, Table 1). Prior to the participating in the study, 19 (51%) patients had received ≥ 2 lines of systemic therapy. At the time of enrollment, 10 (27%) patients were refractory to their previous treatments whereas the remaining patients had relapsed diseases. After the first day of first cycle, all patients completed at least one cycle of treatment. The response rate was determined by the best