Introduction: Understanding the real-world evolution in the multiple myeloma (MM) pathway enhances evidence-based treatment decisions by complementing findings generated from clinical trials.

The objective of this study was to evaluate the evolution of treatment patterns and clinical outcomes in MM patients who began therapy between 2012 and 2023 within the collaborative framework of the HONEUR federated data network.

In this study, we present updated results from a previously published analysis at ASH 2024, featuring extended follow-up and the inclusion of new countries. To date, the HONEUR federated data network has gathered over 80,000 treated MM patients from 27 partners.

Methods: Data from patients starting treatment between 2012–2023 in 10 European MM registries were analyzed: France (IUCT, RHEMCO-Dijon), Germany (TriNetX), Czech Republic (RMG), UK (UHL,Cardiff and Vale), Italy (IRST Meldola), Spain (Hospital Universitario La Fe, Hospital del Mar), and Israel (Sourasky Medical Center). Locally collected patient-level data were uniformly analyzed, and site-specific results were aggregated centrally using the HONEUR federated data network. Patient characteristics and treatment trends were descriptively analyzed. Time to next treatment (TTNT), used as a proxy for progression-free survival, and overall survival (OS) were assessed in 4-year intervals using Kaplan-Meier and proportional hazards regression. A subanalysis was conducted in patients receiving stem cell transplant (SCT).

Results: A total of 30,490 patients with MM initiated frontline therapy from 2012 to 2023, with patients from France (14,851/48.7%), Germany (7946/26.1%), Czech Republic (5934/19.5%), UK (715/2.3%), Israel (604/2.0%), Italy (249/0.8%), and Spain (191/0.6%).

The study cohort included 13% of patients >80 years and 50.6% with ISS stage ≥2, reflecting MM patients treated in real-life clinical practice and including patients ineligible for clinical trials. The study population was distributed into 3 time-based cohorts: 2012–2015 (n=6057), 2016–2019 (n=12,610), and 2020–2023 (n=11,823).

The treatment paradigm significantly evolved during the study period. While IMiD-based regimens remained stable across time periods, PI-based regimens accounted for 45.3% during the first period (2012–2015), and were reduced to 16.7% in the last period (2020–2023), during which use of CD38-based regimens grew to 39.5%. Evolution over time of regimens initiated in frontline differed significantly across countries. Notably, the percentage of CD38-based regimens in the last period was highest in France (62%), followed by Israel (48%). Percentages in Spain and Germany were 31% and 29%, respectively; UK and Italy reported 26% and 18%.

During the study period, median frontline TTNT and OS were 29.2 and 85.7 months, respectively. Across time periods, frontline TTNT increased from median 28.9 months (2012–2015) to 32.4 months (2020–2023; HR 0.86, P<0.001). Median OS improved from 74.1 months (2012–2015) to not reached (2020–2023; HR 0.73, P<0.001).

While some countries had limited or no data recorded in the first period (Germany, Israel, and Spain), outcomes improved over time in France, Germany, Italy, and Spain, coinciding with increased uptake of CD38-based regimens. Other countries exhibited no observed differentiation (Czech Republic and Israel) or a decline (UK) during 2020–2023. These trends may be linked to the COVID-19 pandemic's effects, slower adoption of novel regimens, and differing trends in SCT recommendations.

SCT contributed to significantly improved patient outcomes. Median OS and TTNT were longer in patients receiving SCT (30% of all patients; 138.4 months and 51.1 months) than in those who did not receive SCT (64.2 months and 21.3 months).

OS improvements were seen in the last period vs the first period in both transplanted (HR, 0.58; P<0.001) and nontransplanted patients (HR, 0.63; P<0.001). Similarly, TTNT in the last period improved for both transplanted (HR, 0.64; P<0.001) and non-transplanted patients (HR, 0.79; P<0.001) vs the first period.

Conclusions: With extended follow-up and inclusion of 3 additional European countries, this study consistently highlights an increased adoption of innovative regimens, along with improved TTNT and OS from 2012–2023. The overall results were mainly driven by France and Germany, which contributed the majority of patients analyzed and where uptake of frontline CD38-based regimens is sizeable.

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2025
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