A pooled analysis of more than 10,000 patients with relapsed/refractory (R/R) multiple myeloma, including elderly, advanced disease, and comorbid patients, demonstrated that the effectiveness of ixazomib/lenalidomide/dexamethasone (IRd) in routine clinical practice is comparable to the efficacy of IRd reported in the TOURMALINE-MM1 clinical trial. These findings were reported at ASH by the study’s presenting author Roman Hajek, MD, PhD.
In line with previous real-world data reports, patients treated with IRd in earlier lines of relapse appear to have improved outcomes over patients in later lines, the investigators noted.
Ixazomib, the first oral proteasome inhibitor, has been approved for more than 3 years in some 70 countries for the treatment of R/R multiple myeloma in patients who have received ≥1 prior therapies. Approval was based on the aforementioned phase 3 TOURMALINE-MM1 study, which reported an overall response rate of 78% and median progression-free survival of 20.6 months.
However, outcomes and tolerability in routine clinical practice often differ from data reported in clinical trials for novel agent–based multiple myeloma therapies. About 40% of patients do not meet the standard eligibility criteria to participate in randomized trials, contributing to the disconnect observed between outcomes reported in clinical trials compared with use of a regimen as part of routine clinical practice.
Dr Hajek and colleagues presented an expanded pooled analysis with longer follow-up of IRd from 2 sources: INSIGHT MM, a large, prospective, observational study of more than 4300 patients from the United States, Europe, Israel, Asia, and Latin America, and the Czech Registry of Monoclonal Gammopathies, which has clinical data for more than 6000 patients. The aim was to evaluate the effectiveness of IRd in R/R patients in routine clinical practice.
At the data cutoff of November 22, 2018, the analysis included 217 patients from 11 countries, 89% of whom were treated at academic facilities. The investigators noted that results from academic centers may not be representative of the community practice setting.
At diagnosis, 32% of patients had International Staging System stage III disease, 78% had bone lesions, 46% had anemia, 12% had elevated creatinine, and 21% had extramedullary disease. Prior therapies included bortezomib (90%), stem-cell transplant (60%), thalidomide (47%), lenalidomide (26%), carfilzomib (8%), daratumumab (6%), and pomalidomide (2%). Patients received IRd in the second line (43%), third line (35%), or fourth line and beyond (22%). Median time from diagnosis to start of IRd therapy was 42.1 months, and median age (67 years) was comparable to that seen in the IRd arm of the TOURMALINE-MM1 study (66 years).
For the 152 patients with data on best response to therapy, the objective response rate was 74%, with very good partial responses or better (≥VGPR) achieved by 36% of patients. Response rates for second-, third-, and fourth-line therapy or beyond were 82%, 71%, and 59%, respectively, including ≥VGPRs in 43%, 37%, and 17%, respectively.
Median progression-free survival was 21.6 months across all lines of treatment, and at 12 months 62% of patients were progression-free. At data cutoff, 53 (24%) patients had died. Median overall survival was 36.7 months, with 79% of patients alive at 12 months.
“These findings show that the effectiveness of IRd in routine clinical practice is comparable to the efficacy of IRd reported in the registrational TOURMALINE MM1 trial,” Dr Hajek noted. “IRd is well tolerated with no new safety signals, low rates of dose reductions due to adverse events for ixazomib (10%) and lenalidomide (21%), and similar rates of drug discontinuations due to adverse events reported for ixazomib (44%) and lenalidomide (45%).”
Hajek R, et al. ASH Abstract 1845.