Decrease in early mortality for newly diagnosed multiple myeloma patients in the Netherlands: a population-based study

Mirian Brink,Avinash G Dinmohamed,Pieter Sonneveld,Ellen Van Der Spek,Kaz Groen,Esther De Waal,Niels W C J Van De Donk,Monique C Minnema,Sonja Zweegman,Mark-David Levin,Annemiek Broijl,Paula F Ypma,Eduardus F M Ward Posthuma

doi:10.1038/s41408-021-00571-8

Abstract

Identification of risk factors for early mortality (EM) in multiple myeloma (MM) patients may contribute to different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in EM and risk factors for EM among MM patients diagnosed in the Netherlands. All MM patients, newly diagnosed between 1989 and 2018, were identified in the Netherlands Cancer Registry. Patients were categorized into three calendar periods (1989–1998, 1999–2008, 2009–2018) and into five age groups (≤65, 66–70, 71–75, 76–80, >80 years). EM was defined as death by any cause ≤180 days post-diagnosis. We included 28,328 MM patients (median age 70 years; 55% males). EM decreased from 22% for patients diagnosed in 1989–1998 to 13% for patients diagnosed in 2009–2018 (P < 0.01) and this decrease was observed among all age groups. Exact causes of death could not be elucidated. Besides patient’s age, we found that features related to a more aggressive disease presentation, and patient characteristics reflecting patients’ physical condition were predictive of EM. In summary, EM decreased from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Therefore, novel strategies should be explored to improve the outcome of patients at risk for EM.

Highlights

The introduction of novel agents and autologous stem cell transplantation (SCT) improved the population-level survival of patients with newly diagnosed multiple myeloma (MM)
For cohort 1, we evaluated the impact of age, sex, period of diagnosis, hospital type at diagnosis, and prior malignancies on early mortality (EM) by calculating hazard ratios (HRs) and corresponding 95% confidence intervals using univariable and multivariable Cox proportional regression analysis
We did not observe differences in the use of bortezomib, lenalidomide, daratumumab, or thalidomidecontaining regimens in first-line treatment among patients with or without occurrence of EM, neither when age categories were analyzed separately. In this nationwide, population-based study among patients diagnosed with MM during a 30-year period in the Netherlands, we demonstrate that survival of MM patients improved over time and that the EM rate markedly decreased across all age groups

Summary

Introduction

The introduction of novel agents and autologous stem cell transplantation (SCT) improved the population-level survival of patients with newly diagnosed multiple myeloma (MM). Risk factors for EM that have previously been identified in clinical trials include features related to aggressive disease presentation or high-risk MM and patient-related factors, such as age and comorbid conditions [1,2,3,4]. These clinical trial populations differ substantially from the general MM population due to limited enrollment of frail elderly patients and preclusion of patients with comorbidities or poor performance status at diagnosis [5].

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Methods

Conclusion