Ixazomib plus lenalidomide-dexamethasone improves PFS, OS in multiple myeloma
Combining ixazomib with lenalidomide and dexamethasone improved progression-free survival (PFS) and overall survival (OS) over lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with one to three treatments, according to the China Continuation study.
A total of 115 Chinese patients were randomized to receive ixazomib 4.0 mg (n=57) or placebo (n=58) on days 1, 8, and 15, plus lenalidomide 25 mg (days 1–21) and dexamethasone 40 mg (days 1, 8, 15, and 22) in 28‑day cycles. [J Hematol Oncol 2017;doi:10.1186/s13045-017-0501-4]
The ixazomib-lenalidomide-dexamethasone combination was superior to the lenalidomide-dexamethasone combination in terms of PFS (median 6.7 vs 4.0 months; hazard ratio [HR], 0.598, 95 percent confidence interval [CI], 0.367–0.972; p=0.035) after a median follow-up of 7.4 and 6.9 months for the respective groups.
There was also a significant OS benefit favouring the ixazomib-lenalidomide-dexamethasone combination over lenalidomide-dexamethasone (median 25.8 vs 15.8 months; HR, 0.419, 95 percent CI, 0.242–0.726; p=0.001) after a median follow-up of 20.2 and 19.1 months, respectively.
“[The] OS findings are indicative of a treatment effect rather than an effect driven by imbalances between arms in patient subgroups, subsequent therapies, or non-MM-related deaths,” said the researchers.
Grade ≥3 adverse events (AEs) were reported by 67 and 74 percent of participants in the ixazomib-lenalidomide-dexamethasone and lenalidomide-dexamethasone arms, respectively.
This study was a separate regional extension of the global TOURMALINE-MM1* study. [N Engl J Med 2016;374:1621-1634] However, despite identical eligibility criteria and dosing regimens, median PFS in the current study was lower compared with the global trial.
“[S]ubsequent therapy in China is different from Western populations … [The] differences are likely attributable to the fact that Chinese MM patients present with more advanced stage disease … than patients in other regions,” said the researchers.
Overall, the 4.0 mg/week ixazomib dose combined with lenalidomide-dexamethasone demonstrated a favourable benefit-risk profile in Chinese patients with RRMM, noted the researchers. “[The present] findings provide supportive evidence for the activity, tolerability, and safety of the all-oral triplet regimen of [ixazomib-lenalidomide-dexamethasone] … as a treatment option for patients with RRMM around the world,” they said.
Despite the introduction of advanced treatment options over the last two decades, MM remains incurable. [Leukemia 2014;28:1122-1128] Furthermore, there has been an increasing incidence of MM in Asia, hence the need for further evaluation of new treatment alternatives. [Am J Hematol 2014;89:751-756; Lancet 2016;387:251-272; N Engl J Med 2014;371:906-917; J Clin Oncol 2015;33:3459-3466]
“[S]pecific investigation of … therapies in Asian populations is important in the context of differences in the clinical profile of MM and treatment patterns compared with [therapies] in North America and Europe,” said the researchers.