Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance

• Published in: Internal Medicine Vol. 61; no. 9; pp. 1337 - 1343
• Main Authors: Kakimoto, Yoshihide, Hoshino, Miyako, Hashimoto, Mikiko, Hiraizumi, Masaya, Shimizu, Kohei, Chou, Takaaki
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Internal Medicine 01.05.2022; Japan Science and Technology Agency
• Subjects: Adult; adverse drug reaction; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Boron Compounds; Clinical medicine; Dexamethasone; Dexamethasone - therapeutic use; Diarrhea; Diarrhea - chemically induced; Diarrhea - epidemiology; Gastrointestinal diseases; Glycine - analogs & derivatives; Humans; Internal medicine; ixazomib; Japan; Leukopenia - chemically induced; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - etiology; Nausea; Original; Patients; Peripheral neuropathy; post-marketing all-case surveillance; Product Surveillance, Postmarketing; proteasome inhibitor; Safety; Skin diseases; Surveillance; Thalidomide - therapeutic use; Thrombocytopenia; Thrombocytopenia - chemically induced; Thrombocytopenia - drug therapy; Thrombocytopenia - epidemiology; Japan; multiple myeloma; proteasome inhibitor; adverse drug reaction; safety; ixazomib; post-marketing all-case surveillance
• ISSN: 0918-2918; 1349-7235
• DOI: 10.2169/internalmedicine.7768-21

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance. Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported. Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events). Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.