PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma
| العنوان: | PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma |
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| المؤلفون: | Ivan Borrello, Scott J. Rodig, Gordon J. Freeman, John M. Timmerman, Deepika Cattry, Michael Millenson, Bjoern Chapuy, Ahmad Halwani, Su Y oung Kim, Philippe Armand, Azra H. Ligon, Lili Zhu, Stephen M. Ansell, Stephen J. Schuster, Joseph F. Grosso, Alexander M. Lesokhin, Martin Gutierrez, Emma C. Scott, Margaret A. Shipp |
| المصدر: | New England Journal of Medicine. 372:311-319 |
| بيانات النشر: | Massachusetts Medical Society, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Immunoconjugates, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Antineoplastic Agents, Article, Recurrence, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Humans, Reed-Sternberg Cells, Brentuximab vedotin, Janus Kinases, Brentuximab Vedotin, business.industry, Antibodies, Monoclonal, General Medicine, Immunotherapy, Middle Aged, Programmed Cell Death 1 Ligand 2 Protein, medicine.disease, Hodgkin Disease, Lymphoma, Transplantation, STAT Transcription Factors, Nivolumab, Reed–Sternberg cell, Tumor progression, Immunology, Female, business, Stem Cell Transplantation, medicine.drug |
| الوصف: | BACKGROUND Preclinical studies suggest that Reed–Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin’s lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1–blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin’s lymphoma. METHODS In this ongoing study, 23 patients with relapsed or refractory Hodgkin’s lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression. RESULTS Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed–Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling. CONCLUSIONS Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin’s lymphoma. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT01592370.) |
| تدمد: | 1533-4406 0028-4793 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::73d596be0099fe8102037a58d116af26Test https://doi.org/10.1056/nejmoa1411087Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....73d596be0099fe8102037a58d116af26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15334406 00284793 |
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