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Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to...

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Autores principales: Kaiser, Martin, Beksaç, Meral, Gulbrandsen, Nina, Schjesvold, Fredrik, Hájek, Roman, Moreau, Philippe, de Arriba de la Fuente, Felipe, Mateos, María-Victoria, West, Sharon, Spencer, Andrew, Rajkumar, S. Vincent, Suryanarayan, Kaveri, Czorniak, Michael, Li, Cong, Teng, Zhaoyang, Labotka, Richard, Dimopoulos, Meletios A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340660/
https://www.ncbi.nlm.nih.gov/pubmed/32613281
http://dx.doi.org/10.1007/s00277-020-04149-5
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author Kaiser, Martin
Beksaç, Meral
Gulbrandsen, Nina
Schjesvold, Fredrik
Hájek, Roman
Moreau, Philippe
de Arriba de la Fuente, Felipe
Mateos, María-Victoria
West, Sharon
Spencer, Andrew
Rajkumar, S. Vincent
Suryanarayan, Kaveri
Czorniak, Michael
Li, Cong
Teng, Zhaoyang
Labotka, Richard
Dimopoulos, Meletios A.
author_facet Kaiser, Martin
Beksaç, Meral
Gulbrandsen, Nina
Schjesvold, Fredrik
Hájek, Roman
Moreau, Philippe
de Arriba de la Fuente, Felipe
Mateos, María-Victoria
West, Sharon
Spencer, Andrew
Rajkumar, S. Vincent
Suryanarayan, Kaveri
Czorniak, Michael
Li, Cong
Teng, Zhaoyang
Labotka, Richard
Dimopoulos, Meletios A.
author_sort Kaiser, Martin
collection PubMed
description The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1–4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413
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spelling pubmed-73406602020-07-09 Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma Kaiser, Martin Beksaç, Meral Gulbrandsen, Nina Schjesvold, Fredrik Hájek, Roman Moreau, Philippe de Arriba de la Fuente, Felipe Mateos, María-Victoria West, Sharon Spencer, Andrew Rajkumar, S. Vincent Suryanarayan, Kaveri Czorniak, Michael Li, Cong Teng, Zhaoyang Labotka, Richard Dimopoulos, Meletios A. Ann Hematol Original Article The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1–4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413 Springer Berlin Heidelberg 2020-07-01 2020 /pmc/articles/PMC7340660/ /pubmed/32613281 http://dx.doi.org/10.1007/s00277-020-04149-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Kaiser, Martin
Beksaç, Meral
Gulbrandsen, Nina
Schjesvold, Fredrik
Hájek, Roman
Moreau, Philippe
de Arriba de la Fuente, Felipe
Mateos, María-Victoria
West, Sharon
Spencer, Andrew
Rajkumar, S. Vincent
Suryanarayan, Kaveri
Czorniak, Michael
Li, Cong
Teng, Zhaoyang
Labotka, Richard
Dimopoulos, Meletios A.
Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title_full Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title_fullStr Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title_full_unstemmed Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title_short Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
title_sort adverse event management in the tourmaline-mm3 study of post-transplant ixazomib maintenance in multiple myeloma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340660/
https://www.ncbi.nlm.nih.gov/pubmed/32613281
http://dx.doi.org/10.1007/s00277-020-04149-5
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