Enhancing Multiple Myeloma Treatment Outcomes with Ixazomib: Insights and Perspectives
Authors:   Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania, CONSTANTIN Bianca , BARBU Sanziana ,   Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania, ZIDARU Larisa ,   Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania, CIRLAN Loredana ,   Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania, GAMAN Mihnea ,   "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania, BADELITA Sorina ,   Center of Hematology and Bone Marrow Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania
Published: August 2024

Introduction: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells in the bone marrow, resulting in diverse clinical manifestations. Despite treatment advancements, MM remains incurable, with frequent relapses and therapy resistance. Proteasome inhibitors have revolutionized MM treatment, with ixazomib emerging as a promising oral option. Ixazomib selectively inhibits the 20S proteasome, disrupting the ubiquitin-proteasome pathway crucial for malignant plasma cell survival. Clinical trials demonstrate ixazomib's efficacy and safety, alone or combined with lenalidomide and dexamethasone. Notably, the TOURMALINE-MM1 trial showed improved progression-free survival with ixazomib, establishing its significance in MM therapy. This article comprehensively reviews ixazomib's pharmacological properties, clinical efficacy, safety, and future perspectives in MM management, aiming to enhance therapeutic outcomes in this challenging malignancy. Material and methods. This retrospective study at Fundeni Clinical Institute included 35 multiple myeloma patients treated with Ixazomib over a period of 5 years.Treatment included ixazomib, lenalidomide, and dexamethasone (IRd) for 34 patients.Data analysis assessed treatment response, progression-free survival (PFS), overall survival (OS), and adverse events. This evaluation aims to provide insight into ixazomib-based therapy's efficacy and safety in a predominantly frail patient population. Results. The study included 35 multiple myeloma patients aged 48 to 89, with 33 considered frail. The IRd group achieved an 80% overall response rate, with a median progression-free survival (PFS) of 18 months. Adverse events were common, with gastrointestinal disturbances, fatigue, and peripheral neuropathy being notable. Grade 3/4 adverse events occurred in 57% of patients, leading to dose reductions in 60% of cases. Frail patients showed a 78% response rate and a 1-year overall survival rate of 82%. Overall, ixazomib-based therapy demonstrated efficacy but was associated with manageable adverse events. Conclusion. In summary, our study confirms ixazomib's effectiveness and safety in treating multiple myeloma, especially in elderly and frail patients. With its high response rates and tolerable side effects, ixazomib proves to be a good treatment option for relapse refractory multiple myeloma patients.