Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort.

INTRODUCTION: Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study. PATIENTS: Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+). RESULTS: The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+. CONCLUSION: EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.

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.