UVEA-IXA is a 2-phase, observational, multicenter cohort study of ixazomib-based therapies provided via an early access program in patients with relapsed/refractory multiple myeloma (RRMM) that aimed to assess real-world clinical practice with ixazomib-based therapies. The first phase included a retrospective chart review, and the second phase consisted of a 1-year prospective follow-up with quarterly reporting. The primary end point was effectiveness, including overall response rate (ORR), progression-free survival (PFS), complete response (CR), and very good partial response (VGPR). Secondary end points included patient and disease characteristics, prior therapies, and clinical outcomes by line of ixazomib therapy and cytogenetic risk.
The study included 233 evaluable patients. Patients were included from 44 centers across 8 European countries, including Czech Republic, Great Britain, Greece, Hungary, Italy, Slovakia, Slovenia, and Spain, and had biochemical or symptomatic relapse after 1 to 3 prior therapies. Approximately 35% had received 1 prior therapy, 46% received 2 prior therapies, and 19% received 3 prior therapies. Patients had an Eastern Cooperative Oncology Group performance status of 0-2, and were not refractory to lenalidomide or proteasome inhibitors. Patients ranged from 36 to 92 years, with a median age of 69 years. Approximately one-third of patients had International Staging System stage III disease. Nearly two-thirds of patients had at least 1 comorbidity, with hypertension, renal disease, and diabetes being the most common. The median duration of prior therapies was 10.3 months, with proteasome inhibitors and immunomodulatory agents being the most common; 49% had received a stem-cell transplant. Time to progression following first-line, second-line, and third-line therapies was 17.7 months, 9.7 months, and 11.5 months, respectively. The median time to progression for the most recent therapy was 12 months, with 19%, 23%, and 34% of patients having achieved CR, VGPR, and partial response, respectively. The median study follow-up was 24 months, during which time 42% of patients died. The median duration of ixazomib, lenalidomide, and dexamethasone therapies were 11.1 months, 13.9 months, and 14.1 months, respectively. The ORR was 58%, and the median PFS was 16.2 months. Approximately 23% of patients had a VGPR, whereas 18% had stable disease and 24% had progressive disease.
Approximately 19% of patients taking ixazomib required a dose reduction, which was related to adverse events developing in 15% of patients. The treatment discontinuation rate was 71%, 30% of which was because of disease progression and 16% of which was because of adverse events. Adverse events occurred in 46% of patients, with grade ≥3 adverse events and serious adverse events each affecting 11% of patients. The most common adverse events included thrombocytopenia and diarrhea. The most common grade ≥3 adverse event was thrombocytopenia.
When comparing these results to those in the TOURMALINE-MM1 clinical trial of ixazomib, the UVEA-IXA study included patients who were older, had a higher rate of advanced state disease, and had received more previous lines of therapy. The study supports the effectiveness and tolerability of ixazomib in a real-world setting.
Reference
Abstract and Poster EP976. EHA 2020. June 12, 2020. Ixazomib-based therapy in relapsed/refractory multiple myeloma (MM) patients (pts) treated via an early access program (EAP) in Europe: the ‘use via early access to ixazomib’ (UVEA-IXA) study.