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Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib
Perifosine, an investigational, oral, synthetic alkylphospholipid, inhibits signal transduction pathways of relevance in multiple myeloma (MM) including PI3K/Akt. Perifosine demonstrated anti‐MM activity in preclinical studies and encouraging early‐phase clinical activity in combination with bortezo...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175725/ https://www.ncbi.nlm.nih.gov/pubmed/35847734 http://dx.doi.org/10.1002/jha2.4 |
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author | Richardson, Paul G. Nagler, Arnon Ben‐Yehuda, Dina Badros, Ashraf Hari, Parameswaran N. Hajek, Roman Spicka, Ivan Kaya, Hakan LeBlanc, Richard Yoon, Sung‐Soo Kim, Kihyun Martinez‐Lopez, Joaquin Mittelman, Moshe Shpilberg, Ofer Blake, Paul Hideshima, Teru Colson, Kathleen Laubach, Jacob P. Ghobrial, Irene M. Leiba, Merav Gatt, Moshe E. Sportelli, Peter Chen, Michael Anderson, Kenneth C. |
author_facet | Richardson, Paul G. Nagler, Arnon Ben‐Yehuda, Dina Badros, Ashraf Hari, Parameswaran N. Hajek, Roman Spicka, Ivan Kaya, Hakan LeBlanc, Richard Yoon, Sung‐Soo Kim, Kihyun Martinez‐Lopez, Joaquin Mittelman, Moshe Shpilberg, Ofer Blake, Paul Hideshima, Teru Colson, Kathleen Laubach, Jacob P. Ghobrial, Irene M. Leiba, Merav Gatt, Moshe E. Sportelli, Peter Chen, Michael Anderson, Kenneth C. |
author_sort | Richardson, Paul G. |
collection | PubMed |
description | Perifosine, an investigational, oral, synthetic alkylphospholipid, inhibits signal transduction pathways of relevance in multiple myeloma (MM) including PI3K/Akt. Perifosine demonstrated anti‐MM activity in preclinical studies and encouraging early‐phase clinical activity in combination with bortezomib. A randomized, double‐blind, placebo‐controlled phase 3 study was conducted to evaluate addition of perifosine to bortezomib‐dexamethasone in MM patients with one to four prior therapies who had relapsed following previous bortezomib‐based therapy. The primary endpoint was progression‐free survival (PFS). The study was discontinued at planned interim analysis, with 135 patients enrolled. Median PFS was 22.7 weeks (95% confidence interval 16·0–45·4) in the perifosine arm and 39.0 weeks (18.3–50.1) in the placebo arm (hazard ratio 1.269 [0.817–1.969]; P = .287); overall response rates were 20% and 27%, respectively. Conversely, median overall survival (OS) was 141.9 weeks and 83.3 weeks (hazard ratio 0.734 [0.380–1.419]; P = .356). Overall, 61% and 55% of patients in the perifosine and placebo arms reported grade 3/4 adverse events, including thrombocytopenia (26% vs 14%), anemia (7% vs 8%), hyponatremia (6% vs 8%), and pneumonia (9% vs 3%). These findings demonstrate no PFS benefit from the addition of perifosine to bortezomib‐dexamethasone in this study of relapsed/refractory MM, but comparable safety and OS. |
format | Online Article Text |
id | pubmed-9175725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91757252022-07-14 Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib Richardson, Paul G. Nagler, Arnon Ben‐Yehuda, Dina Badros, Ashraf Hari, Parameswaran N. Hajek, Roman Spicka, Ivan Kaya, Hakan LeBlanc, Richard Yoon, Sung‐Soo Kim, Kihyun Martinez‐Lopez, Joaquin Mittelman, Moshe Shpilberg, Ofer Blake, Paul Hideshima, Teru Colson, Kathleen Laubach, Jacob P. Ghobrial, Irene M. Leiba, Merav Gatt, Moshe E. Sportelli, Peter Chen, Michael Anderson, Kenneth C. EJHaem Haematologic Malignancy–Plasma Cell Perifosine, an investigational, oral, synthetic alkylphospholipid, inhibits signal transduction pathways of relevance in multiple myeloma (MM) including PI3K/Akt. Perifosine demonstrated anti‐MM activity in preclinical studies and encouraging early‐phase clinical activity in combination with bortezomib. A randomized, double‐blind, placebo‐controlled phase 3 study was conducted to evaluate addition of perifosine to bortezomib‐dexamethasone in MM patients with one to four prior therapies who had relapsed following previous bortezomib‐based therapy. The primary endpoint was progression‐free survival (PFS). The study was discontinued at planned interim analysis, with 135 patients enrolled. Median PFS was 22.7 weeks (95% confidence interval 16·0–45·4) in the perifosine arm and 39.0 weeks (18.3–50.1) in the placebo arm (hazard ratio 1.269 [0.817–1.969]; P = .287); overall response rates were 20% and 27%, respectively. Conversely, median overall survival (OS) was 141.9 weeks and 83.3 weeks (hazard ratio 0.734 [0.380–1.419]; P = .356). Overall, 61% and 55% of patients in the perifosine and placebo arms reported grade 3/4 adverse events, including thrombocytopenia (26% vs 14%), anemia (7% vs 8%), hyponatremia (6% vs 8%), and pneumonia (9% vs 3%). These findings demonstrate no PFS benefit from the addition of perifosine to bortezomib‐dexamethasone in this study of relapsed/refractory MM, but comparable safety and OS. John Wiley and Sons Inc. 2020-04-06 /pmc/articles/PMC9175725/ /pubmed/35847734 http://dx.doi.org/10.1002/jha2.4 Text en © 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Haematologic Malignancy–Plasma Cell Richardson, Paul G. Nagler, Arnon Ben‐Yehuda, Dina Badros, Ashraf Hari, Parameswaran N. Hajek, Roman Spicka, Ivan Kaya, Hakan LeBlanc, Richard Yoon, Sung‐Soo Kim, Kihyun Martinez‐Lopez, Joaquin Mittelman, Moshe Shpilberg, Ofer Blake, Paul Hideshima, Teru Colson, Kathleen Laubach, Jacob P. Ghobrial, Irene M. Leiba, Merav Gatt, Moshe E. Sportelli, Peter Chen, Michael Anderson, Kenneth C. Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title | Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title_full | Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title_fullStr | Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title_full_unstemmed | Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title_short | Randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
title_sort | randomized, placebo‐controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib |
topic | Haematologic Malignancy–Plasma Cell |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175725/ https://www.ncbi.nlm.nih.gov/pubmed/35847734 http://dx.doi.org/10.1002/jha2.4 |
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