What Is the Benefit of Autologous Stem Cell Transplantation in Multiple Myeloma Beyond the Age of 65? Inputs from Real-World Data in the Emmy Cohort

Background The management of newly diagnosed multiple myeloma (NDMM) patients under 70 years of age, in good health condition and without comorbidities, is based on an induction therapy followed by high-dose therapy with autologous stem cell transplantation (ASCT) and maintenance (1). Several studies have demonstrated this regimen to be effective up to 65 years of age (2). Beyond this age, patients are often excluded from clinical trials and few real-world evidence studies are available. The EMMY study, a large-scale real-world study designed to assess the epidemiology and real-life management of MM, describes the use of ASCT in patients aged of 65 and over and its efficacy compared to other treatments.

Methods EMMY is a non-interventional, prospective study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of 800 to 1000 additional patients each year (3616 patients included at the end of 2020). Data are updated annually from hospital records up to 2021.

NDMM patients aged 65 years and over, who received a front-line therapy with ASCT (ASCT+), were identified and described. Progression-free survival (PFS) (median and rates at 36 and 48 months (m)), time to next treatment (TTNT) (median and rates at 36m and 48m) and overall survival (OS) rates at 36m and 48m were described for ASCT+ patients ≥65 years and compared to ASCT+ patients <65 years identified in EMMY (Wilcoxon test). ASCT+ patients ≥65 years were also compared with non-autologous transplant patients (ASCT-) of the same age ([65-75[ years). Same analyses were conducted for the subgroup of ASCT+ / ASCT- patients aged of 66-70 years.

Results Among the 1597 NDMM patients enrolled in EMMY, 156 NDMM patients ≥65 years of age received a first-line therapy with ASCT; 129 (82.7%) had less than 70 years and 27 beyond (17.3%). Patients were male (55.1%), without comorbidities (72.4%) with an ECOG of 0 or 1 (89.4%) and an ISS score of 1, 2, 3 for 30.3%, 39.4% and 30.3% of them. For those patients, mPFS was estimated at 47.7m (95 CI% [34.4 to not reached]) with 36m and 48m PFS rates estimated at 56.1% (95 CI% [46.2; 66.0]) and 48.6% (95 CI% [37.0; 60.3]). mTTNT was not reached while 36m and 48m TTNT rates were 67.6% (95 CI% [57.7; 77.4]) and 57.4% (95 CI% [45.3; 69.4]). Regarding OS, 36m and 48m rates were 96.2% (95 CI% [92.8; 99.5]) and 89.3% (95 CI% [81.0; 97.6]).

Survival outcomes for ASCT+ patients aged ≥65 years did not differ from those for ASCT+ patients aged <65 years (n=397 in EMMY) for PFS (p=0.32), TTNT (p=0.54), and OS (p=0.54). ASCT+ patients aged ≥ 65 years had similar characteristics (M/F ratio, ECOG, ISS, comorbidities) than ASCT+ patients aged <65 years.

Compared with ASCT- patients of same age (n=397), ASCT+ patients aged ≥65 years had higher survival outcomes with a significant improvement in PFS (mPFS of 47.7m vs. 19.4m and 36m rates of 56.1% vs. 32.8%, p<0.0001, Figure 1), in TTNT (mTTNT not achieved vs 23.4m in ASCT- patients and 36m rates of 67.6% vs. 34.7%, p<0.0001); and in OS (36m rates of 96.5% vs. 74.0%, p=0.0013). ASCT+ patients aged ≥ 65 years had a median age of 67.5 years (vs. 70.8 years), ECOG 0-1 for 89.4% (vs. 69.0%), comorbidities for 27.6% (vs. 44.3%) and ISS II or III for 69.7% (vs. 76.4%) compared to ACST- patients aged ≥65 years.

Same comparisons performed with the 66-70 years subgroup of ASCT+ (n=105) and ASCT- (n=192) patients confirmed previous survival outcomes results in terms of PFS (mPFS of 47.5m vs 20.6m, p=0.0004), TTNT (p<0.0001) and OS (p=0.0002).

Conclusion These results are among the first estimates of the higher efficacy of ASCT in selected patients aged 65 years and over. Almost half patients (46.2%) up to 70 years of age received ASCT as first-line therapy, less frequently (about 10%) beyond. Although the use of ASCT is usually reserved to healthy patients, its clinical benefit over 65 years is significant in terms of survival and equivalent to that observed in younger patients.

Perrot:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria. Decaux:GSK: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Gilead: Honoraria; BMS: Honoraria; Janssen: Honoraria. Belhadj Merzoug:BMS, Janssen, Sanofi, Amgen, Abbvie: Consultancy, Honoraria, Other: Travel for ASH, ASCO and EHA annual meetings. Sonntag:BMS: Consultancy; Janssen: Consultancy. Moreau:AbbVie, Janssen, Celgene, Amgen, and Sanofi: Honoraria. Texier:Kappa Sante: Current Employment. Hulin:Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; GSK: Honoraria; BMS: Honoraria; Janssen: Honoraria.