Retrospective analysis of using ixazomib in patients with relapsed/refractory multiple myeloma
Multiple myeloma (MM) remains incurable relapsing disease and novel agents are under investigation in order to prolong progression-free and overall survival of MM patients (pts). Ixazomib is the first oral proteasome inhibitor that showed effectiveness in relapsed/refractory MM. Patients (pts) refractory to prior bortezomib therapy are often responsive to ixazomib treatment. As newly introduced agent, ixazomib requires further investigation.
Patients and methods
Retrospective analysis of a single-center experience was performed in 12 pts with MM. Efficacy and tolerability of ixazomibe-based regimen was assessed. These patients were treated with ixazomib between December 2016 and July 2018 in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation. All of them had at list one prior line therapy and relapsed or refractory disease. Response to treatment was assessed according to International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma (Kumar et al., 2016). 11 pts (92%) received IRd treatment regimen (ixazomib+ lenalidomide+ dexamethasone) and 1 patient was treated with prednisolone instead of dexamethasone. Median age was 65.5 (44-75) years at the time of diagnosis, and 70 (48-76) at the start of IRd treatment. 67% (n=8) were males. To assess impact of prior lenalidomide therapy and number of prior treatments on overall response rate (ORR) and rate of complete response (CR) and very good partial response (VGPR) univariate analysis was performed using Chi-square tests for categorical variables.
The median follow-up was 10 months. Median treatment cycles (range) was 8 (2-17). Overall response rate was 58% (n=7), of which 8% (n=1) had CR, 17% (n=2) had VGPR, 33% (n=4) had partial response (PR) as best response. 3 pts (25%) were considered to have stable disease and 2 pts (17%) showed the disease progression. Median (range) time to response was 3 (1-8) months and median (range) response duration was 7 (2-13) months. Eleven patients (92%) had, at least, one adverse event. 5 (42%) developed anemia: 2 (17%) had grade 3 anemia), 6 (50%) had thrombocytopenia (2 pts with grade 4); 4 (33%) had neutropenia: 2 (17%), with grade 3-4; 1 patient (8%) exhibited grade 1 diarrhea, and 3 patients (25%) had upper respiratory tract infections. 33% (n=4) of the patients had adverse events (grade ≥3). Before IRd, 6 pts had multiple lines of treatment including lenalidomide and 6 pts were lenalidomide-naïve and received only one line of treatment. Difference in ORR was not statistically significant between patients with multiple lines of previous treatment (ORR=33%, n=2), and cases with one line of prior therapy (ORR=87%, n=5) (p=0.079), but CR and VGPR rate were significantly higher in the group who received IRd as second-line treatment (0% vs 50%, p=0.046).
Ixazomib-based treatment showed good efficacy (ORR=58%) and acceptable toxicity. Patients without prior lenalidomide and one prior line of treatment had statistically significant improvement in VGPR and CR rate. From this basis, it can be assumed that use of IRd regimen as the second-line therapy may improve depth of response in relapsed/refractory multiple myeloma patients.
Multiple myeloma, relapsed, refractory, ixazomib, efficiency.