Evolution of Treatment Patterns and Survival Outcomes in European Patients with Multiple Myeloma from 2012-2023 through the Honeur Federated Data Network

Introduction: Treatment options for multiple myeloma (MM) have changed significantly over the last decade, largely driven by the results of phase 3 clinical trials. The ability to demonstrate similar improvements in the real world can enhance the validity of evidence-based treatment decisions by supplementing these clinical trial data. Here, we assess how treatment patterns and clinical outcomes have evolved in patients with MM who started treatment between 2012 and 2023 within the HONEUR federated data network.

Methods: Data from patients who started treatment for MM in 5 European registries were explored (IUCT [France], TriNetX Oncology GmbH [Germany], RMG [Czech Republic], UHL [UK], Cardiff and Vale [UK]). Locally stored patient-level data were uniformly analyzed, and site-specific aggregate results were pooled at a central level using the HONEUR federated data network. Patient characteristics and treatment patterns were analyzed. Time to next treatment (TTNT; used as proxy for progression-free survival) and overall survival (OS) were calculated by 4-year time periods using Kaplan-Meier and proportional hazards regression.

Results: From 2012 to 2023, 28,210 patients with MM initiated frontline therapy, with patients from France (51%), Germany (25%), Czech Republic (21%), and the UK (2%). The study cohort included 12% of patients over 80 years of age and 34% with Eastern Cooperative Oncology Group performance status ≥2. The study population was distributed into 3 time-defined cohorts: 2012-2015 (n=5856), 2016-2019 (n=11,954), and 2020-2023 (n=10,400). The utilization of frontline treatment regimens evolved over time and differed significantly across countries. In France, the most frequently used frontline therapy changed from PI-only (31%) or PI-IMiD (47%) regimens before 2020 to anti-CD38–containing regimens (64%) from 2020 onwards. In Germany, the percentage of patients treated with PI-only decreased from 65% before 2020 to 33%, while post 2020, 26% of patients received anti-CD38 combinations. In the Czech Republic and UK, most patients received PI-IMiD regimens post 2020 (70% and 58%, respectively) versus PI-only or IMiD-only regimens before; frontline anti-CD38 treatment was not available in either country. The overall medians for frontline TTNT and OS across the entire time period were 29.1 and 85.5 months, respectively, but were significantly longer in France (41.4 and 117.5 months, respectively) compared with the Czech Republic (23.5 and 52.5 months, respectively) and the UK (17.2 and 39.9 months, respectively). Country-specific trends were seen when investigating consequences of change in treatment patterns on outcomes. Improved outcomes (TTNT and OS) were observed over time in France and Germany only, while outcomes in the 2020-2023 period did not improve (Czech Republic and UK). However, when combining data from all countries, frontline TTNT improved from the 2012-2015 (median, 29.6 months) period to the 2020-2023 (median, 33.1 months; HR, 0.84 vs 2012-2015; P<0.001) period. Similarly, OS across countries improved between the 2012-2015 (median, 75.0 months) and 2020-2023 (median, not reached) (HR, 0.78 vs 2012–2015; P<0.001) period.

Conclusions: Across all countries, improved frontline TTNT and OS was observed from 2012 to 2023, which coincided with a change in treatment regimens. The observed improvement in outcomes was driven by data from France and Germany, which is likely related to availability of PI-IMiD combinations and the emergence of anti-CD38 therapies for frontline treatment in both countries.