Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma
| Autor: | Jasmine Zain, Robert Orlowski, Philippe Armand, Guilherme Fleury Perini, Arun Balakumaran, Jakub Svoboda, Jing Ouyang, Pier Luigi Zinzani, Pei-Hsuan Chen, Vincent Ribrag, Catherine Thieblemont, Vladimir Melnichenko, Gayane Tumyan, Azra H. Ligon, Gilles Salles, Margaret A. Shipp, Maria D Caballero, Muhit Ozcan, Beth Christian, Zafer Gulbas, Donna Neuberg, Jan Walewski, Robert A. Redd, Arkendu Chatterjee, Sanjay R. Patel, Sergio Portino, Scott J. Rodig, Kamal Bouabdallah, Laura Fogliatto |
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| Přispěvatelé: | Armand, Philippe, Rodig, Scott, Melnichenko, Vladimir, Thieblemont, Catherine, Bouabdallah, Kamal, Tumyan, Gayane, Özcan, Muhit, Portino, Sergio, Fogliatto, Laura, Caballero, Maria D, Walewski, Jan, Gulbas, Zafer, Ribrag, Vincent, Christian, Beth, Perini, Guilherme Fleury, Salles, Gille, Svoboda, Jakub, Zain, Jasmine, Patel, Sanjay, Chen, Pei-Hsuan, Ligon, Azra H, Ouyang, Jing, Neuberg, Donna, Redd, Robert, Chatterjee, Arkendu, Balakumaran, Arun, Orlowski, Robert, Shipp, Margaret, Zinzani, Pier Luigi |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Poor prognosis Lymphoma B-Cell Time Factors Pembrolizumab Antibodies Monoclonal Humanized Mediastinal Neoplasms Risk Assessment Unmet needs Young Adult Antineoplastic Agents Immunological Refractory Risk Factors Internal medicine Hematologic Malignancy medicine Humans Primary Mediastinal Large B-Cell Lymphoma Progression-free survival Pembrolizumab Relapsed Refractory Primary Mediastinal Large B-Cell Lymphoma business.industry ORIGINAL REPORTS Middle Aged South America medicine.disease Progression-Free Survival United States Lymphoma Europe Editorial Commentary Drug Resistance Neoplasm Monoclonal Disease Progression Female Neoplasm Recurrence Local business |
| Zdroj: | Journal of Clinical Oncology Ann Transl Med |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade. METHODS In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692 ) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990 ) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity. RESULTS The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival. CONCLUSION Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL. |
| Databáze: | OpenAIRE |
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