Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10)
| العنوان: | Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10) |
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| المؤلفون: | F. Hitz, M. Kraus, T. Pabst, D. Hess, L. Besse, T. Silzle, U. Novak, K. Seipel, S. Rondeau, S. Stüdeli, S. Berardi Vilei, P. Samaras, U. Mey, C. Driessen, for the Swiss Group for Clinical Cancer Research SAKK |
| المصدر: | Blood Cancer Journal, Vol 9, Iss 9, Pp 1-8 (2019) Hitz, F; Kraus, M; Pabst, Thomas; Hess, D; Besse, L; Silzle, T; Novak, Urban; Seipel, Katja; Rondeau, S; Stüdeli, S; Vilei, S Berardi; Samaras, P; Mey, U; Driessen, C (2019). Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10). Blood cancer journal, 9(9), p. 70. Springer Nature 10.1038/s41408-019-0228-2 <http://dx.doi.org/10.1038/s41408-019-0228-2> Blood Cancer Journal |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Cell biology, Anti-Inflammatory Agents, 610 Medicine & health, Peripheral blood mononuclear cell, Gastroenterology, lcsh:RC254-282, Article, Dexamethasone, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Adverse effect, Lenalidomide, Multiple myeloma, Pneumonitis, Aged, Aged, 80 and over, Nelfinavir, business.industry, Bortezomib, Hematology, HIV Protease Inhibitors, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer therapeutic resistance, Oncology, 030220 oncology & carcinogenesis, Female, business, Multiple Myeloma, 030215 immunology, medicine.drug |
| الوصف: | The antiretroviral agent nelfinavir has antimyeloma activity and can overcome resistance to bortezomib. Our phase I/II trial investigated whether adding nelfinavir to lenalidomide–dexamethasone can overcome lenalidomide resistance in lenalidomide-refractory multiple myeloma (MM). Twenty-nine patients were included (high-risk cytogenetic aberrations 31%; ≥2 prior therapy lines 93%; lenalidomide–bortezomib double-refractory 34%). Twenty-four patients (83%) had prior bortezomib and 10 (34%) were lenalidomide–bortezomib double-refractory. They received four cycles of nelfinavir 2500 mg/day with standard-dose lenalidomide (25 mg days 1–21) and dexamethasone (40/20 mg days 1, 8, 15, 22). Minor response or better was achieved in 16 patients (55%; 95% CI 36–74%), including 40% of those who were lenalidomide–bortezomib double-refractory, and partial response or better in nine patients (31%; 95% CI 15–51%). Median progression-free survival was 3.4 (95% CI 2.0–4.9) months and median overall survival 21.6 (13.0–50.1) months. Lenalidomide-related pneumonitis, pneumonia, and neutropenic fever occurred, but there were no unexpected adverse events. Peripheral blood mononuclear cells showed a 45% (95% CI 40–51%) reduction in total proteasome activity from baseline and significant induction of unfolded protein response and autophagy. Thus, nelfinavir–lenalidomide–dexamethasone is an active oral combination in lenalidomide-refractory MM. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2044-5385 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b09dcc16e1fd8629234b44651d327686 http://link.springer.com/article/10.1038/s41408-019-0228-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b09dcc16e1fd8629234b44651d327686 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20445385 |
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