Background: Multiple myeloma (MM) is a plasma cell malignancy that primarily affects older adults, with the median age of diagnosis being 69 years. Around 35% of people with MM are diagnosed at age 75 or older, and 10% are diagnosed at age 85 or older. Autologous stem cell transplant (ASCT) remains a standard treatment for eligible younger patients, but its role in the elderly population is less clear, particularly with recent advancements in therapeutic options and the scarcity of phase 3 clinical trials that include patients over the age of 65. This study aims to analyze the impact of ASCT on elderly MM patients using a large database.

Methods: We performed a retrospective analysis by utilizing the TriNetX platform to leverage real-world patient data and aggregate electronic medical records from 89 healthcare organizations predominantly based in the US. We identified patients ≥65 years of age that had been diagnosed with MM over three time periods; namely prior to January 1, 2015, between 2015 and 2020, and on or after January 1, 2021. Patients were divided into two cohorts based on whether they underwent ASCT. Propensity score matching was performed on 17 characteristics, including demographics (age, gender, race), comorbidities (diabetes, lipidemias, hypertensive and ischemic heart diseases, chronic kidney disease), medications (insulin, blood glucose regulation agents, platelet aggregation inhibitors), and BMI. The cohorts were analyzed for 5-year overall survival (OS), early mortality, risk of developing myeloid malignancies, risk of falls, and ED visits between years 1 and 5 from diagnosis as measures of frailty. Outcomes were identified using ICD codes and evaluated using Kaplan-Meier survival analysis, measures of association, and risk analysis for various clinical endpoints.

Results: We identified 18,667, 31,764, and 35,180 patients diagnosed before 2015, between 2015 and 2020, and after 2020, respectively. Among them, 21%, 16%, and 12% have undergone ASCT, respectively. After propensity matching, we included 3,756, 4,939, and 4,132 patients in each cohort over consecutive diagnosis eras. Hazard ratios (HR) for 5-year OS for ASCT vs. no ASCT groups showed improvement over time in favor of the ASCT group: 0.862 (0.789-0.941) (before 2015), 0.689 (0.635-0.747) (2015-2020), and 0.578 (0.507-0.658) (after 2020), all with significant p-values (p=0.000). OS HRs similarly improved: 0.956 (0.895-1.022) (before 2015), 0.753 (0.699-0.812) (2015-2020), and 0.571 (0.500-0.651) (after 2020), all with significant p-values (p=0.000). The risk of early mortality (within 1 year of diagnosis) was consistently lower in the ASCT group across all eras, with risk ratios of 0.615 (0.525-0.720) (before 2015), 0.511 (0.444-0.589) (2015-2020), and 0.620 (0.527-0.729) (after 2020).

The risk of developing myeloid malignancies increased for ASCT patients in all eras, with risk ratios of 3.630 (3.060-4.308) (before 2015), 3.757 (3.150-4.482) (2015-2020), and 4.695 (3.506-6.288) (after 2020). We calculated the risk of falls and ED visits from 1 to 5 years after diagnosis as a surrogate for frailty. ASCT patients had higher risk ratios for falls: 2.033 (1.643-2.515) (before 2015), 1.762 (1.544-2.010) (2015-2020), and 1.779 (1.350-2.344) (after 2020). ASCT patients also had higher risk ratios for ED visits: 1.911 (1.716-2.129) (before 2015), 1.486 (1.396-1.581) (2015-2020), and 1.750 (1.530-2.001) (after 2020).

Conclusion: Despite advancements in treatment, ASCT continues to offer significant survival benefits for the elderly patient newly diagnosed with MM. The benefit of ASCT over other treatment regimens has increased over time, with reduced early mortality and improved overall survival benefit. However, the increased risk of developing myeloid malignancies and frailty post-ASCT highlights the need for careful patient selection and poses the question of how we define transplant eligibility in this patient population. Our analysis offers a real-world, real-time perspective on the safety and survival benefit of ASCT in the elderly population when compared to those treated without ASCT. These findings support the rationale for considering ASCT in elderly patients, contingent on thorough pre-transplant evaluation.

Disclosures

No relevant conflicts of interest to declare.

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2024
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