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Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma

In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients...

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Autores principales: Krishnan, Amrita, Kapoor, Prashant, Palmer, Joycelynne M., Tsai, Ni-Chun, Kumar, Shaji, Lonial, Sagar, Htut, Myo, Karanes, Chatchada, Nathwani, Nitya, Rosenzweig, Michael, Sahebi, Firoozeh, Somlo, George, Duarte, Lupe, Sanchez, James F., Auclair, Daniel, Forman, Stephen J., Berdeja., Jesus G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005710/
https://www.ncbi.nlm.nih.gov/pubmed/32082000
http://dx.doi.org/10.1038/s41375-018-0038-8
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author Krishnan, Amrita
Kapoor, Prashant
Palmer, Joycelynne M.
Tsai, Ni-Chun
Kumar, Shaji
Lonial, Sagar
Htut, Myo
Karanes, Chatchada
Nathwani, Nitya
Rosenzweig, Michael
Sahebi, Firoozeh
Somlo, George
Duarte, Lupe
Sanchez, James F.
Auclair, Daniel
Forman, Stephen J.
Berdeja., Jesus G.
author_facet Krishnan, Amrita
Kapoor, Prashant
Palmer, Joycelynne M.
Tsai, Ni-Chun
Kumar, Shaji
Lonial, Sagar
Htut, Myo
Karanes, Chatchada
Nathwani, Nitya
Rosenzweig, Michael
Sahebi, Firoozeh
Somlo, George
Duarte, Lupe
Sanchez, James F.
Auclair, Daniel
Forman, Stephen J.
Berdeja., Jesus G.
author_sort Krishnan, Amrita
collection PubMed
description In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll 3 additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ≥partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ≥stable disease. The most common adverse events (≥grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.
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spelling pubmed-60057102018-06-18 Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma Krishnan, Amrita Kapoor, Prashant Palmer, Joycelynne M. Tsai, Ni-Chun Kumar, Shaji Lonial, Sagar Htut, Myo Karanes, Chatchada Nathwani, Nitya Rosenzweig, Michael Sahebi, Firoozeh Somlo, George Duarte, Lupe Sanchez, James F. Auclair, Daniel Forman, Stephen J. Berdeja., Jesus G. Leukemia Article In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll 3 additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ≥partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ≥stable disease. The most common adverse events (≥grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM. 2018-02-23 2018-07 /pmc/articles/PMC6005710/ /pubmed/32082000 http://dx.doi.org/10.1038/s41375-018-0038-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Krishnan, Amrita
Kapoor, Prashant
Palmer, Joycelynne M.
Tsai, Ni-Chun
Kumar, Shaji
Lonial, Sagar
Htut, Myo
Karanes, Chatchada
Nathwani, Nitya
Rosenzweig, Michael
Sahebi, Firoozeh
Somlo, George
Duarte, Lupe
Sanchez, James F.
Auclair, Daniel
Forman, Stephen J.
Berdeja., Jesus G.
Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title_full Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title_fullStr Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title_full_unstemmed Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title_short Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
title_sort phase i/ii trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005710/
https://www.ncbi.nlm.nih.gov/pubmed/32082000
http://dx.doi.org/10.1038/s41375-018-0038-8
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