Tags

Type your tag names separated by a space and hit enter

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.
Ann Hematol. 2020 Aug; 99(8):1793-1804.AH

Abstract

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.

Authors+Show Affiliations

Department of Haematology, The Royal Marsden Hospital, London, UK. Martin.Kaiser@icr.ac.uk. Division of Molecular Pathology, The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, 123 Old Brompton Road, London, SW7 3RP, UK. Martin.Kaiser@icr.ac.uk.Department of Hematology, Ankara University, Ankara, Turkey.Oslo Myeloma Center, Oslo University Hospital, and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway.Oslo Myeloma Center, Oslo University Hospital, and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway.Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic.Department of Hematology, University Hospital Hôtel-Dieu, Nantes, France.Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer y Centro Regional de Hemodonación, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain.Department of Hematology, University Hospital of Salamanca, CIC, IBM CC, Salamanca, Spain.Department of Haematology, The Royal Marsden Hospital, London, UK.Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia.Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.Hematology and Medical Oncology, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

32613281

Citation

Kaiser, Martin, et al. "Adverse Event Management in the TOURMALINE-MM3 Study of Post-transplant Ixazomib Maintenance in Multiple Myeloma." Annals of Hematology, vol. 99, no. 8, 2020, pp. 1793-1804.
Kaiser M, Beksaç M, Gulbrandsen N, et al. Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. Ann Hematol. 2020;99(8):1793-1804.
Kaiser, M., Beksaç, M., Gulbrandsen, N., Schjesvold, F., Hájek, R., Moreau, P., de Arriba de la Fuente, F., Mateos, M. V., West, S., Spencer, A., Rajkumar, S. V., Suryanarayan, K., Czorniak, M., Li, C., Teng, Z., Labotka, R., & Dimopoulos, M. A. (2020). Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. Annals of Hematology, 99(8), 1793-1804. https://doi.org/10.1007/s00277-020-04149-5
Kaiser M, et al. Adverse Event Management in the TOURMALINE-MM3 Study of Post-transplant Ixazomib Maintenance in Multiple Myeloma. Ann Hematol. 2020;99(8):1793-1804. PubMed PMID: 32613281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. AU - Kaiser,Martin, AU - Beksaç,Meral, AU - Gulbrandsen,Nina, AU - Schjesvold,Fredrik, AU - Hájek,Roman, AU - Moreau,Philippe, AU - de Arriba de la Fuente,Felipe, AU - Mateos,María-Victoria, AU - West,Sharon, AU - Spencer,Andrew, AU - Rajkumar,S Vincent, AU - Suryanarayan,Kaveri, AU - Czorniak,Michael, AU - Li,Cong, AU - Teng,Zhaoyang, AU - Labotka,Richard, AU - Dimopoulos,Meletios A, Y1 - 2020/07/01/ PY - 2020/05/12/received PY - 2020/06/14/accepted PY - 2020/7/3/pubmed PY - 2020/7/14/medline PY - 2020/7/3/entrez KW - Adverse events KW - Ixazomib KW - Maintenance therapy KW - Multiple myeloma KW - Safety SP - 1793 EP - 1804 JF - Annals of hematology JO - Ann. Hematol. VL - 99 IS - 8 N2 - 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. SN - 1432-0584 UR - https://www.unboundmedicine.com/medline/citation/32613281/Adverse_event_management_in_the_TOURMALINE-MM3_study_of_post-transplant_ixazomib_maintenance_in_multiple_myeloma L2 - https://dx.doi.org/10.1007/s00277-020-04149-5 DB - PRIME DP - Unbound Medicine ER -