China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ixazomib (NinlaroTM), developed by Takeda, gained approval from the FDA in 2015 for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma (Figure 6.85). In the UK it is recommended by NICE for multiple myeloma patients who have received at least one prior therapy (in combination with lenalidomide and dexamethasone). It is distinguished from bortezomib and carfilzomib in that it can be administered orally which is a significant advantage in terms of patient convenience and overall cost of treatment.Structure of ixazomib (NinlaroTM).
Multiple Myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Ixazomib maintenance as a weekly tablet also improves PFS compared to placebo although this is likely inferior to lenalidomide maintenance.44 Maintenance strategies with daratumumab will become more attractive once daratumumab hopefully moves to a subcutaneous route.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Other proteasome inhibitors used for treating multiple myeloma in adults are the related drug carfilzomib (blocking the proteasome irreversibly) and Ixazomib (above scheme). The latter has been approved by the FDA in November 2015 and by the EMA in November 2016. It acts by a mechanism similar to that of Bortezomib but is the first orally administered proteasome inhibitor and is combined with Lenalidomide (derivative of thalidomide, above scheme; the cytotoxic effects of Ixazomib and Lenalidomide enforce each other mutually) and Dexamethasone (above scheme) to counter certain side effects.
An update on the safety of ixazomib for the treatment of multiple myeloma
Published in Expert Opinion on Drug Safety, 2022
Given the oral route of administration, gastrointestinal toxicities are common with ixazomib-based regimens. In Phase I studies, nausea was reported in as high as 38%-42% of patients, although majority of these adverse events were Grade 1 and 2 [38,50]. In the TOURMALINE-MM1 trial, the rates of nausea and vomiting were higher with IRd versus placebo-Rd (nausea - 29% vs. 22%, vomiting - 23% vs. 12%) [41]. Dose reductions due to nausea were seen in <2% in IRd <1% placebo-Rd receiving patients [79]. A similar trend was seen in NDMM patients (TOURMALINE-MM2, any grade nausea - 37% vs. 27%, vomiting - 29.7% vs. 13.2% in IRd vs. placebo-Rd), and in the maintenance setting (TOURMALINE-MM 3: nausea - 39% vs. 15%, vomiting - 27% vs. 11%; TOURMALINE-MM4: nausea - 26.8% vs. 8% for IRd vs. placebo-Rd) [65,76,78]. In all the above trials, the difference in the rates of nausea between the two groups was largely driven by low-grade AEs.
Efficacy and safety of ixazomib maintenance therapy for patients with multiple myeloma: a meta-analysis
Published in Hematology, 2021
Huixian Chen, Yongjing Wang, Chunchun Shao, Chenxi Sun, Chengyun Zheng
Ixazomib (Ninlaro®) is a highly selective reversible protease inhibitor approved by FDA for treatment of relapsed or refractory multiple myeloma (RRMM) in combination with lenalidomide and dexamethasone (IRd). In TOURMALINE-MM1, a global phase III clinical study, ixazomib showed therapeutic superiority over placebo regimens for all individuals including high-risk patients [9]. Patients resistant to bortezomib often showed responses to ixazomib [10]. As the first oral dosage form of PI, ixazomib plays an important and positive role in improving the convenience of medication and helping patients return to social life. Currently, several clinical trials have been conducted with some results on ixazomib maintenance. In order to determine the efficacy and safety, it is necessary to systematically integrate the existing research results, namely, to study its impact on survival outcomes of MM patients by systematic evaluation and meta-analysis, and to provide guidance for the selection of clinical maintenance treatment options.
Ixazomib for the treatment of multiple myeloma
Published in Expert Opinion on Pharmacotherapy, 2018
Paul G. Richardson, Sonja Zweegman, Elizabeth K. O’Donnell, Jacob P. Laubach, Noopur Raje, Peter Voorhees, Renda H. Ferrari, Tomas Skacel, Shaji K. Kumar, Sagar Lonial
The first oral PI ixazomib is now an established component of the RRMM treatment armamentarium, demonstrating strong anti-myeloma activity and a well-tolerated and manageable toxicity profile. Encouraging data have been reported in patients with a particularly poor prognosis and largest unmet medical need, including those with high-risk cytogenetic abnormalities, elderly/frail patients, and those treated with multiple prior therapies. Ixazomib has been shown to be a valuable combination partner with multiple different anti-myeloma agents in a range of different regimens in a number of clinical studies. Combined with the limited additional toxicity and maintained patient-reported QoL, the oral administration of ixazomib may offer a simpler, less burdensome, and sustained PI therapy for many patients.