Background: The prognosis of multiple myeloma (MM) has improved considerably in recent years owing to the introduction of novel agents. However, it remains unclear whether these therapeutic advancements confer similar survival benefits in patients aged ≥80 years. Clinical trials for MM often exclude patients aged ≥80 years, limiting the generalizability of results in this age group. Given the aging population in Japan and worldwide, it is crucial to evaluate whether recent therapeutic advances can benefit elderly patients in real-world clinical settings.

Methods: We retrospectively analyzed the overall survival (OS) of 300 patients diagnosed with MM at our institution between 2007 and 2023. Patients were divided into two cohorts: an early era (2007–2014, n=122) and a later era (2015–2023, n=178). Subgroup analyses were performed for younger (age <80 years) and elderly (age ≥80 years) patients. Deaths due to MM were defined as those occurring after disease progression, assessed using the International Myeloma Working Group criteria. Non-MM-related deaths were defined as deaths due to any other cause. Overall survival (OS) was estimated using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. The cumulative incidence of MM-related and non-MM-related deaths was assessed using Gray's test, considering competing risks. This study was approved by the ethics committee of Yamanashi Prefectural Central Hospital and was conducted in accordance with the tenets of the Declaration of Helsinki.

Results: The overall patient cohort had a median age of 74 years (range, 41–93 years), and 34 patients had an Eastern Cooperative Oncology Group performance status (PS) of 2 or higher. There were no statistically significant differences between the early and later eras in terms of median age, sex, PS, or disease stage at diagnosis.

With a median follow-up of 2.4 years, the 2-year OS rate improved significantly from 51.8% in the early era to 73.7% in the later era (log-rank p=2.26×10−7). The cumulative mortality due to MM progression decreased from 26.2% to 12.8% at 2 years (Gray's test, p=4.06×10−3). The non-MM-related cumulative mortality also declined from 21.9% to 13.5% (Gray's test, p=0.006) over the same periods.

Among patients aged <80 years, the 2-year cumulative mortality due to MM decreased from 24.2% to 12.6% (p=0.0305), as did the non-MM-related mortality (from 18.9% to 8.8%, p=1.23×10−3), indicating significant improvements in both categories.

By contrast, among patients aged ≥80 years, MM-related 2-year mortality improved significantly from 34.4% to 13.8% (p=0.046). Non-MM-related mortality remained high and unchanged (35.0% vs. 27.4%, p=0.619), with no statistical significance.

Among 158 observed deaths, the primary causes included MM progression (n=67), infection (n=30), heart failure (n=26), renal failure (n=14), secondary malignancies (n=8), cerebrovascular events (n=4), interstitial pneumonia (n=2), and other diseases (n=7).

Conclusions:

Our analysis demonstrated that the introduction of novel therapeutic agents has led to improved OS among patients with MM, including both those aged <80 and ≥80 years. The favorable outcomes observed in the later era likely reflect the increased use of novel agents—mainly daratumumab, isatuximab, carfilzomib, elotuzumab, and pomalidomide—which only became available in Japan after 2015. Despite these advancements, MM-related mortality remains the leading cause of death. In those aged <80 years, both MM-related and non-MM-related mortality declined significantly over time. By contrast, in patients aged ≥80 years, although MM-related mortality showed clear improvement, non-MM-related mortality remained essentially unchanged. These findings indicate that non-MM causes of death continue to be an important barrier to further improving outcomes in elderly patients. Future strategies should focus on mitigating non-MM-related mortality by tailoring treatment intensity and more proactively addressing comorbidities.

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2025
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