EARLY MORTALITY AMONG patients with NEWLY DIAGNOSED MULTIPLE MYELOMA IN THE NETHERLANDS: a population-based study
The introduction of novel agents and autologous stem cell transplantation improved the population-level survival of patients with multiple myeloma (MM). However, early mortality (EM) remains a major clinical issue. Identification of risk factors of EM may contribute to more rigorous supportive care measures or different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in and risk factors of EM among MM patients diagnosed in the Netherlands during a 30-year period.
All MM patients diagnosed between 1989-2018—with survival follow-up through 2020—were identified from the Netherlands Cancer Registry. Primary end point was EM defined as the date from MM diagnosis to all-cause death ≤180 days. Patients were categorized into three calendar periods (1989-1998, 1999-2008, 2009-2018) and four age groups (≤65, 66-70, 71-80, >80 years). The impact of age, sex, period of diagnosis, hospital type at diagnosis and prior malignancies for EM was evaluated using uni- and multivariable Cox regression analyses. Moreover, for patients diagnosed in 2014-2018, detailed data on type of paraprotein, thrombocytopenia, serum albumin, serum β2-microglobulin, cytogenetic risk, calcium, renal failure, anemia and bone lesions at baseline was evaluated. P<0.05 indicates statistical significance.
Our analytical cohort included 28,328 MM patients (median age 70 years, age range 25-99; 55% males; 88% diagnosed in non-academic centers; 13% with prior malignancies). Median age and proportions of hospital type at diagnosis, and prior malignancies were similar across the three calendar periods. In 2009-2018, a higher proportion of male patients was observed as compared to 1989-1998 (57% vs. 52%; P<0.001).
EM for patients ≤65 was 11%, 11%, and 6% (P<0.001) in 1989-1998, 1999-2008, and 2009-2018, respectively. The corresponding proportions for patients aged 66-70 were 19%, 16%, and 8% (P<0.001), for patients 71-80, 25%, 22%, and 15% (P<0.001), and for patients >80, 40%, 41%, and 31% (P<0.001). When simultaneously adjusted for calendar period, sex, age, hospital type at diagnosis and prior malignancies, patients diagnosed in 2009-2018 had a 42% lower risk of mortality as compared with patients diagnosed in 1989-1998 (hazard ratio, 0.58; P<0.001) with an adverse effect of older age and prior malignancies.
In 2014-2018, 6.380 MM patients were diagnosed of whom 780 (12%) patients died ≤180 days post-diagnosis. Albumin <35 g/L, β2-microglobulin ≥3.5 mg/L, thrombocytopenia, hypercalcemia, and poor renal function have an adverse effect on EM for patients ≤70. In addition, anemia and bone lesions ≥1 have an adverse effect on EM for patients >70.
In summary, EM among MM patients improved from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Patients at risk for EM may benefit from better supportive care or individualized anti-MM therapy.