<p>Effective Treatment with PD-1 Antibody, Chidamide, Etoposide, and Thalidomide (PCET) for Relapsed/Refractory Natural Killer/T-Cell Lymphoma: A Report of Three Cases</p>

Abstract

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is a specific subtype of peripheral T cell lymphoma (PTCL) with a poor prognosis. To date, there exist no standard therapeutic regimens for relapsed/refractory (R/R) ENKTL. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R ENKTL. Herein, we present three R/R ENKTL patients who failed prior therapies (L-asparaginase containing chemotherapy, radiotherapy or biological-cell therapy, etc.) benefited from the combination regimen comprised of anti-programmed-death-1 (PD-1) antibody toripalimab, chidamide, etoposide, and thalidomide. They received the treatment regimen continuously until the disease progression occurs. As of data collection, two patients achieved complete remission (CR) after 4, 6 cycles of treatment, respectively, and another patient was evaluated as partial remission (PR) after 2 cycles. Treatment-related adverse events (AEs) mainly presented grade 2~3 leukocytopenia and anemia, which were controllable. It follows that PD-1 antibody, chidamide, etoposide, and thalidomide (PCET) regimen may be a promising choice for patients with R/R ENKTL and warrants further investigation.

SMARCA2 deficiency in NSCLC: a clinicopathologic and immunohistochemical analysis of a large series from a single institution

“…Blaszczak et al [ 31 ] and McCaw et al [ 32 ] have also verified that HDACis can upregulate tumor antigen expression, increase the number and cytotoxicity of NK and CD8+ cells to enhance cellular immunity, and thus increase the antitumor effects in vivo and in vitro, suggesting that there will be a synergistic effect if they are combined in antitumor therapy. For the application of HDACis in combination with ICIs in antitumor therapy, researchers have conducted preliminary studies in soft tissue sarcoma [ 33 ] and lymphoma [ 34 ] and achieved good results. At present, there are no studies of HDACis combined with ICIs therapy in lung cancer.…”

Chemorefractory extranodal nasal-type natural-killer/T-cell lymphoma with great response to pembrolizumab in a young patient: a case report

“…Novel immunotherapies are considered for advanced-stage or relapsed/refractory ENKTCL (Table 1 ) [ 9 – 11 ]. Given that programmed death ligand 1 (PD-L1) is expressed in a substantial portion of ENKTL, it is an important biomarker that is widely used for patient selection for immunotherapy [ 12 ]. Pembrolizumab blocks PD-L1 owing to EBV-driven overexpression of the latent membrane proteins [latent membrane protein 1 (LMP1) and LMP2] with activation of the NF-κB/MAPK pathways [ 13 ].…”

Progress in the treatment of NK-cell lymphoma/leukemia

“…Further assessments of factors affecting the response to PD-1/PD-L1 antibodies are needed to identify the appropriate population for those treatments. More recently, the combination of several chemotherapies with immune checkpoint inhibitors has also been evaluated and has demonstrated promising results [77][78][79] . In particular, a phase Ib/II trial of the combination of sintilimab, a PD-1 antibody, and chidamide, a histone deacetylase (HDAC) inhibitor, in 36 relapsed or refractory ENKL patients showed superior ORR and CR rates of 58% and 44%, respectively [77] .…”

“…More recently, the combination of several chemotherapies with immune checkpoint inhibitors has also been evaluated and has demonstrated promising results [77][78][79] . In particular, a phase Ib/II trial of the combination of sintilimab, a PD-1 antibody, and chidamide, a histone deacetylase (HDAC) inhibitor, in 36 relapsed or refractory ENKL patients showed superior ORR and CR rates of 58% and 44%, respectively [77] . Further analyses are warranted to identify the best combination therapy for ENKL patients.…”