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
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Pabst, Thomas Niklaus, Novak, Urban, Seipel, Katja |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2044-5385 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Rebeka Gerber |
Date Deposited: |
31 Oct 2019 11:12 |
Last Modified: |
02 Mar 2023 23:32 |
Publisher DOI: |
10.1038/s41408-019-0228-2 |
PubMed ID: |
31455773 |
BORIS DOI: |
10.7892/boris.134265 |
URI: |
https://boris.unibe.ch/id/eprint/134265 |
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