Improved survival in myeloma patients-a nationwide registry study of 4,647 patients ≥75 years treated in Denmark and Sweden

Abstract

The prevalence of multiple myeloma (MM) is increasing in Nordic countries and the rest of the western world. Patients aged ≥75 years at diagnosis constitute an increasing proportion of all MM patients, but are underrepresented in randomized clinical trials. There is an urgent need for studies of the characteristics, treatment and outcome in this cohort. We present data from two nationwide population-based registries of all MM patients diagnosed in Denmark from January 1, 2005 until February 18, 2020, and in Sweden from January 1, 2008 until December 31, 2019, including treatment data for patients diagnosed until 2018 (Denmark) and 2019 (Sweden). In total 4,647 patients were ≥75 years at diagnosis, compared to 7,378 younger patients. Patients ≥75 years, accounting for approximately 40% of all MM patients, are a distinct cohort with more advanced disease at diagnosis, reflected by higher International Staging System (ISS) stage, and a higher proportion have renal failure and anemia. We found a more gradual introduction of modern medications in the older cohort than in the younger, despite simultaneous changes in guidelines. Compared to the cohorts in randomized controlled trials that guide the treatment of non-transplant eligible patients, we found a higher proportion of patients ≥75 years and presenting with ISS III in the real-world populations. Nevertheless, response rates and survival are increasing, indicating that modern treatment regimens are effective and well tolerated also in elderly MM patients in real-world populations.

Figure 1.

Prevalence (numbers per 100,000) of plasma cell neoplasms. (A) Patients <75 years at diagnosis in Denmark 1962-2018 and Sweden 1980-2018. (B) Patients ≥75 years at diagnosis in Denmark 1962-2018 and Sweden 1980-2018. Data from the NORDCAN database of the Association of the Nordic Cancer Registries May 3, 2021. The increasing prevalence is particularly evident in the older cohort. In Denmark the prevalence increased from 77.7 to 151.2 per 100,000 men aged ≥75 years, and from 53.33 to 112 per 100,000 women ≥75 years 2005-2018. In Sweden the prevalence increased from 92.7 to 134.2 per 100,000 in men aged ≥75 years, and from 99.3 to 151.2 per 100,000 women ≥75 years from 2008 to 2018.

Figure 2.

Changes in first-line treatment over time for patients ≥75 years in (A) Denmark and (B) Sweden. Cd: cyclophosphamide, dexamethasone; CRd: cyclophosphamide, lenalidomide, dexamethasone; CTd: cyclophosphamide, thalidomide, dexamethasone; Mono: monotherapy; MP: melphalan, prednisolone; MPR: melphalan, prednisolone, lenalidomide; MPT: melphalan, prednisolone, thalidomide; MPV: melphalan, prednisolone, bortezomib; Rd: lenalidomide, dexamethasone; Td: thalidomide, dexamethasone; Td-ixa: thalidomide, dexamethasone, ixazomib; VCd: bortezomib, cyclophosphamide, dexamethasone; Vd: bortezomib, dexamethasone; VRd: bortezomib, lenalidomide, dexamethasone; VTd: bortezomib, thalidomide, dexamethasone.

Figure 3.

Use of immunomodulatory drugs and/or proteasome inhibitors in first-treatment line of multiple myeloma by country and age group. In 2009 the Danish treatment guidelines changed to recommending bortezomib and dexamethasone (VD) in first line for patients eligible for autologous stem cell transplant (ASCT) and melphalan, prednisolone and thalidomide (MPT) or melphalan, prednisolone and bortezomib (MPV) for those ineligible (marked by the red vertical line). In Sweden, the treatment guidelines changed in 2010 (blue vertical line). Bortezomib and thalidomide were recommended as part of standard induction treatment before ASCT. MPT was recommended as standard for patients not eligible for ASCT, while MPV and melphalan and prednisolone were treatment options.

Figure 4.

Response rate for very good partial remission or beter by country and age group. From 2013, multiple myeloma patients ≥75 years are gradually approaching the high response rates on first-line treatment seen among younger patients. Simultaneously, the proportion of non-responders decreased significantly from 57.9% in 2005 to 32.2% in 2019 in Denmark, and from 38% to 16.8% from 2008 to 2019 in Sweden (Online Supplementary Table S4). VGPR: very good partial remission.

Figure 5.

Overall survival by country and age group. (A, B) Overall survival of patients with multiple myeloma in Denmark 2005-2018 (A) and Sweden 2008-2019 (B). mo: months.

Figure 6.

Relative survival by country and age group. (A, B) Relative survival of patients