title: PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase.
abstract: Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including l-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3+CD4+and CD3+CD8+T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing l-asparaginase regimens.
authors.affiliation: Department of Medicine, Queen Mary Hospital, Hong Kong.
authors.forename: Yok-Lam
authors.identifier: 0000-0001-8156-6978
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: Department of Medicine, Queen Mary Hospital, Hong Kong.
authors.forename: Thomas S Y
authors.initials: TSY
authors.lastname: Chan
authors.affiliation: Raffles Cancer Center, Raffles Hospital, Singapore.|Department of Haematology, Singapore General Hospital, Singapore.
authors.forename: Daryl
authors.initials: D
authors.lastname: Tan
authors.affiliation: Division of Haematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Hematology/Oncology, National University Cancer Institute, Singapore.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Poon
authors.affiliation: Mow Blood and Cancer Clinic, Mount Elizabeth Medical Center, Singapore.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mow
authors.affiliation: Department of Diagnostic Radiology, and.
authors.forename: Pek-Lan
authors.initials: PL
authors.lastname: Khong
authors.affiliation: Department of Pathology, Queen Mary Hospital, Hong Kong; and.
authors.forename: Florence
authors.initials: F
authors.lastname: Loong
authors.affiliation: Department of Pathology, Queen Mary Hospital, Hong Kong; and.
authors.forename: Rex
authors.initials: R
authors.lastname: Au-Yeung
authors.affiliation: Department of Anatomic Pathology, Singapore General Hospital, Singapore.
authors.forename: Jabed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Raffles Cancer Center, Raffles Hospital, Singapore.|Department of Haematology, Singapore General Hospital, Singapore.
authors.forename: Colin
authors.initials: C
authors.lastname: Phipps
authors.affiliation: Department of Medicine, Queen Mary Hospital, Hong Kong.
authors.forename: Eric
authors.initials: E
authors.lastname: Tse
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001215:Asparaginase / Q000627:therapeutic use; D004279:DNA, Viral / Q000037:antagonists & inhibitors*; D020031:Epstein-Barr Virus Infections / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D000072230:Sustained Virologic Response; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014184:Transplantation, Homologous; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab; D001215:Asparaginase