title: Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma.
abstract: Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow-up were 7.0 (1.4-10.6) months and 9.8 (6.0-11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4-96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression-free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8-79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Dai
authors.identifier: http://orcid.org/0000-0003-0654-6920
authors.initials: D
authors.lastname: Maruyama
authors.affiliation: Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Fukuhara
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Hematology and Oncology, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Department of Hematology and Oncology, Tokai University, Isehara, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Terui
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Hematology and Oncology, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology and Oncology, Tokai University, Isehara, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shirasugi
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D044466:Asian People; D000079963:Brentuximab Vedotin; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012074:Remission Induction / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; D000079963:Brentuximab Vedotin
keywords: Hodgkin lymphoma; Japanese; immunotherapy; nivolumab; programmed death-1