A study published in Internal Medicine evaluated the safety profile of ixazomib in a cohort of Japanese patients with relapsed/refractory multiple myeloma (MM).
Ixazomib is a proteasome inhibitor improved in both the US and Japan in combination with other therapies for the treatment of relapsed/refractory MM. In order to investigate this treatment, the researchers conducted a nationwide, retrospective, observational study in Japan. The study cohort included every patient in Japan who was treated with ixazomib plus lenalidomide and dexamethasone for relapsed/refractory MM between May and September 2017. Patients were monitored through the completion of the sixth treatment cycle or until treatment discontinuation. The primary outcomes were the patients’ treatment courses, including any adverse events (AEs) that occurred.
In total, 741 patients were analyzed (median age, 71, range=35-92) with a median of three prior lines of treatment prior to the study period (range=1-30). Overall, 279 patients completed all treatment cycles and 461 discontinued treatment after a median of two cycles.
Regarding AEs, more than three-quarters of patients (77.2%; n = 572) experienced adverse drug reactions (ADRs), including 193 patients (26.0%) who experienced serious ADRs. The most common were thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Ten percent of serious ADRs were thrombocytopenia, and 5.9% were diarrhea.
“Approximately half of the patients in this study had thrombocytopenia, compared with 31% reported in the [TOURMALINE-MM 1] study. One possible reason for this difference is that the current study included patients who had platelet counts of <75,000/mm3; in the MM1 study, such patients were not eligible,” the authors commented. “A second contributory factor may have been that the proportion of patients 65 years old was higher in this study than in the MM1 study.”
For this analysis, the researchers pre-specified thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy as ADRs of clinical importance. The incidence of these ADRs at grade ≥3 was 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively.
Forty-nine patients discontinued treatment due to thrombocytopenia, and 43 discontinued due to severe gastrointestinal disorders. Eleven patients died due to ADRs.
In conclusion, the authors wrote, “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.”