Změna prognózy nemocných s mnohočetným myelomem v průběhu 60 let v souboru 1 492 neselektovaných nemocných z oblasti střední a zčásti i severní Moravy

The change of prognosis of 1,492 nonselected patients with multiple myeloma during 60 years in the Middle and partially in the North Moravia region

Objectives: To analyze the development of overall survival (OS), early mortality (EM), and 1 , 5 , and 10 year survival from the diagnosis of multiple myeloma (MM) as a result of advances in anti myeloma and supportive treatments in patients from Central and Northern Moravia over six decades, including evaluation of the impact of age on treatment outcomes and disease prognosis. Materials and Methods: A retrospective analysis was conducted on an unselected cohort of 1,492 patients with symptomatic MM treated at the University Hospital in Olomouc between 1959 and 2022. Median OS was estimated using Kaplan-Meier analysis, and EM was defined as death occurring within one year of diagnosis. Results: A significant and sustained increase in median OS was observed across the predefined time intervals, both in the full patient cohort and in the subgroup aged ≤ 65 years, while improvements among patients older than 65 years were largely non significant. In the pre chemotherapy era (1959–1963), when treatment was purely symptomatic, median OS was 8 months for the total cohort, 9 months for those ≤ 65 years, and only 4 months in the > 65-year group. With the introduction of unsystematic MP regimen therapy (1963–1975), median OS increased to 19, 23, and 10 months in the respective age groups. The era of combined polychemotherapy (1976–1995) saw further gains, with median OS reaching 39, 46, and 32 months. From 1996 to 2010, during which high dose therapy with autologous peripheral hematopoietic cell transplantation (VDT ATPKB) was implemented alongside bortezomib, lenalidomide, and pomalidomide, median OS rose to 45 months overall, 60 months for those ≤ 65, and 30 months for patients older than 65. In the most recent period (2011–2022), characterized by the partial introduction of carfilzomib, daratumumab, and ixazomib, these figures further improved to 54, 95, and 36 months, respectively. In transplant eligible patients under 70 years, median OS reached 114 months during 2011–2022, whereas non transplant eligible individuals treated with conventional therapies achieved a median OS of only 56 months. Early mortality decreased most markedly in younger age groups: comparing the earliest period (1959–1963) with 2011–2016, EM fell from 83.3%, 72.7% and 60.0% in the ≤ 60, 61–70, and > 70 age groups to 4.9%, 12.0%, and 38.2%, respectively. Similarly, the proportions of patients surviving at 1, 5 and 10-years post-diagnosis increased substantially between the early (1959–1963) and later (1996–2010) eras. Among those aged ≤ 60 years, survival rose from 16.7%, 0.0%, and 0.0% to 85.6%, 54.3%, and 32.2%; for patients aged 61–70, from 27.3%, 0.0%, and 0.0% to 79.1%, 39.0%, and 15.4%; and among seniors over 70, from 40.0%, 0.0%, and 0.0% to 72.9%, 25.2%, and 6.9%. Conclusion: Over a span of six decades in the evaluated Moravian region, median OS increased nearly sixfold for the entire cohort and up to tenfold in patients aged ≤ 65, while early mortality declined fourfold. There was also a substantial rise in 1 and 5-year survival rates. A strong age dependent relationship with both OS and EM was confirmed, pointing to the urgent need for further refinement of therapeutic strategies, especially for patients over 70.

Keywords:

Multiple myeloma – overall survival – antimyeloma therapy – early mortality – 1-, 5- and 10-years survival – relationship of age and survival