Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study
| Autor: | Monique C. Minnema, Margaret A. Shipp, Stephen M. Ansell, Nishitha Reddy, Scott J. Rodig, Jonathon B. Cohen, Selda Samakoglu, Kazunobu Kato, Margaretha G.M. Roemer, Sarit Assouline, Philippe Armand, Anne Sumbul, Michelle Poon, Peter Johnson, Azra H. Ligon, Manish Sharma, John M. Timmerman, Andrew Grigg |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Oncology Diffuse/drug therapy Cancer Research Time Factors Lymphoma Programmed Cell Death 1 Receptor Phases of clinical research Transplantation Autologous/adverse effects Clinical Trial Phase II Antineoplastic Agents Immunological immune system diseases hemic and lymphatic diseases Immunological/adverse effects 80 and over Treatment Failure Non-U.S. Gov't Aged 80 and over Research Support Non-U.S. Gov't Programmed Cell Death 1 Receptor/antagonists & inhibitors Remission Induction Hematopoietic Stem Cell Transplantation ORIGINAL REPORTS Middle Aged Clinical Trial Progression-Free Survival Phase II Multicenter Study Nivolumab Lymphoma Large B-Cell Diffuse/drug therapy Disease Progression Female Lymphoma Large B-Cell Diffuse Chromosomes Human Pair 9 Human Pair 9 Antineoplastic Agents Immunological/adverse effects Adult medicine.medical_specialty Autologous/adverse effects Antineoplastic Agents Research Support Transplantation Autologous Chromosomes N.I.H Young Adult Research Support N.I.H. Extramural Refractory Internal medicine Large B-Cell Journal Article medicine Humans Autologous transplantation Progression-free survival Hematopoietic Stem Cell Transplantation/adverse effects Aged Transplantation business.industry Extramural Nivolumab/adverse effects medicine.disease business Diffuse large B-cell lymphoma |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37(6), 481. American Society of Clinical Oncology |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.18.00766 |
| Popis: | Purpose Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. Methods In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. Results Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. Conclusion Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|