Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study.

Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). The REMIX study is one of the largest prospective, real-world analysis of the effectiveness of IXA-Rd in the setting of RRMM. Conducted in France between August 2017 and October 2019, the REMIX study, a non-interventional prospective study, included 376 patients receiving IXA-Rd in second line or later and followed for at least 24 months. Primary endpoint was the median progression-free survival (mPFS). Median age was 71 years (Q1-Q3 65.0 - 77.5) with 18.4% of participants older than 80 years. IXA-Rd was initiated in L2, L3 and L4 + for 60.4%, 18.1% and 21.5%, respectively. mPFS was 19.1 months (95% CI [15.9, 21.5]) and overall response rate (ORR) was 73.1%. mPFS was 21.5, 21.9 and 5.8 months in patients receiving IXA-Rd as L2, L3, L4 + respectively. Among patients receiving IXA-Rd in L2 and L3, mPFS was similar for patients previously exposed to lenalidomide (19.5 months) than for those lenalidomide naive (not exposed, 22.6 months, p = 0.29). mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older (p = 0.06) with similar ORR (72.4% and 76.8%) in both subgroups. Adverse events (AEs) were reported in 78.2% of patients including 40.7% of treatment-related AE. IXA discontinuation was due to toxicity in 21% of patients. To conclude, the results of the REMIX study are consistent with the results of Tourmaline-MM1 and confirm the benefit of IXA-Rd combination in real life. It shows the interest of IXA-Rd in an older and frailer population, with an acceptable effectiveness and tolerance.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma.

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.