Sintilimab Plus Chidamide for Relapsed/Refractory (R/R) Extranodal Nk/T Cell Lymphoma (Enktl): A Prospective, Multicenter, Single‐arm, Phase Ib/Ii Trial (Scent)

Abstract

DLT) during cycle 1. Six dose levels were planned. The CRM design allowed more rapid accrual: once the maximum 3 patients were on the dose level under evaluation, further patients received the dose level below, with all data contributing to dose decisions. Ph 2 used a single stage A'Hern design to assess best ORR during the first 8 cycles (assessed using the Revised Response Criteria for Malignant Lymphoma) of the combination in all participants (pts) treated at the MTD. ROMI was given IV on days 1, 8 and 15 of a 28d cycle; CAR IV on days 1, 2, 8, 9, 15 and 16. HR23B expression was performed on formalin fixed paraffin embedded tissue.Results: 33 pts enrolled to Ph 1 with 27 evaluable for MTD assessment. 34 pts were treated at the MTD and evaluable for Ph 2. Median age 62y (22-82y); 69% male; median prior treatment lines 2 performance status 0 (44%), 1 (44%) or 2 (10%) (1 unknown); 53% refractory to last treatment. 51% had PTCL Not Otherwise Specified; 40% angioimmunoblastic T-cell lymphoma. 7 DLTs were seen in 6 patients during phase 1. The MTD was defined as ROMI 10 mg/m 2 with CAR 20mg/m 2 for 2 doses then 40mg/m 2 , giving an estimated posterior DLT probability of 0.216 with a 90% credible interval (0.106, 0.352). The ORR at the MTD was 32% (95% confidence interval 19-49%): 15% complete response, 18% partial response, 18% stable disease. Grade 3/4 adverse events in ≥ 10% pts were anaemia (17%); neutropenia (35%); thrombocytopenia (42%). Median PFS was 4.0 months (median follow up 19 months); 4 participants remain on treatment. HR23B expression was not associated with response with 27% (3 of 11) HR23B positive pts responding.

Sintilimab and Chidamide for Refractory Transformed Diffuse Large B Cell Lymphoma: A Case Report and A Literature Review

“…In this case, the patient experienced only hematologic adverse events, including thrombocytopenia and neutropenia, without immune-related adverse events and severe adverse events. Compared to the previous safety profiles of a phase I/Ib study of PD-1 antibody pembrolizumab plus HDACi vorinostat for non-small cell lung cancer and a phase Ib/II trial of sintilimab plus chidamide for NK/T cell lymphoma, the treatment-related adverse events of this case were consistent with the observations of previous findings, without additional toxicity appearing ( 28 , 30 , 31 ). These findings indicated that the combination of sintilimab and chidamide has a favorable safety profile.…”

“…Two case reports on NK/T cell lymphoma have reported that combined sintilimab and chidamide therapy may lead to successful outcomes ( 28 , 29 ). Moreover, a phase IB/II trial that included 38 patients with R/R extranodal NK/T cell lymphoma who were treated with sintilimab plus chidamide showed an ORR of 59.5% and a CR rate of 48.6% ( 30 ). Although HDACi plus PD-1 antibody treatment is rarely studied in lymphoma, it is often studied in head and neck squamous cell carcinomas, salivary gland cancer, non-small cell lung cancer, and other types of cancer ( 31 , 32 ).…”

A Prospective Phase II Study of Pegaspargase-COEP Plus Radiotherapy in Patients With Newly Diagnosed Extra-Nodal NK/T-Cell Lymphoma

“…These results were in line with published data showing greater survival benefit with transplant for patients with high-risk ENKTL (24). An alternative solution is the combination of chemotherapy with novel targeted agents such as PD-1 antibodies, histone deacetylase inhibitors or CD30-antibody conjugates (25)(26)(27). In a phase 2 trial, PD-1 antibody monotherapy produced an ORR of 68% and 1-year OS of 82% in patients with relapsed/refractory ENKTL (25).…”

“…In a phase 2 trial, PD-1 antibody monotherapy produced an ORR of 68% and 1-year OS of 82% in patients with relapsed/refractory ENKTL (25). Other clinical trials have reported promising early results of the combination of a PD-1 antibody with a histone deacytelase inhibitor for relapsed/refractory ENKTL (27). Although these agents have not yet been tested in the first-line setting, it is hopeful that results from these trials might eventually change the treatment landscape of ENKTL towards a more riskadapted and individualized approach.…”

Case Report: Outcome and Adverse Events of Anti-PD-1 Antibody Plus Chidamide for Relapsed/Refractory Sézary Syndrome: Case Series and A Literature Review

“…Although anti-PD-1 antibodies or HDACi were associated with modest ORR and duration time when used as a single agent in R/R CTCL, several case reports and clinical studies have shown an enhanced effect of the combination of chidamide plus sintilimab in R/R NK/T cell lymphoma (NKTCL) ( 47 , 48 ). A phase IB/II trial including 38 patients with R/R extranodal NKTCL showed an ORR of 59.5% and a CR rate of 48.6% with a durable response ( 49 ). Moreover, this combination therapy has also achieved efficacy in patients with other types of tumors ( 50 , 51 ).…”