Plasma cell malignancies in Sweden : subgroup descriptions and regional outcomes for multiple myeloma

Abstract

Plasma cell disorders appear in various forms such as aggressive plasma cell leukemia (PCL), typical symptomatic multiple myeloma (MM), non-symptomatic smouldering multiple myeloma (SMM) and solitary plasmacytoma (SP). The different entities all require specific considerations regarding diagnosis and treatment. MM can be further characterized by secretion of M protein, CRAB features (elevated calcium, renal impairment, anemia, bone lesions) and cytogenetic aberrations. New methods and markers, such as serum free light chains (S-FLC), cytogenetics and skeletal surveys with CT and MRI, now enable the clinicians to approach MM with a different set of diagnostic possibilities than before.

The aim of this thesis is to investigate the outcome in SP and PCL as well as in the oligo and non-secretory MM subgroups, referred to in study II as non-measurable MM. We also aim to describe outcome and treatment for MM patients in the six healthcare regions in Sweden. Data was retrospectively collected from the Swedish Myeloma register for all three studies.

In study I, data from patients with solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) were analyzed in comparison with MM. Progression to MM, described by cumulative incidence function (CIF), at two-years was more frequent for SBP than EMP (35% compared to 7%). However, relative survival was not better for EMP than for SBP. Patients in the study with primary PCL had a poor prognosis with no patients being alive 5 years after diagnosis. In study II, data from patients with oligo and non-secretory MM were studied and presented in subgroups based on secretion of M protein in serum and urine as well as serum free light chains (S-FLC). True non secretory MM (with no elevated secretion of S-FLC and M protein) constituted only 6% of patients with available S-FLC. No differences in overall survival (OS) were seen between secretory and non-measurable MM disease, or between secretory MM and the non-measurable MM subgroups. In study III, we saw differences in survival between healthcare regions in Sweden for MM patients, with a better survival in region A. For patients eligible for autologous stem cell transplantation (ASCT) there was also a better survival in region A in comparison with other regions. The difference persisted also in multivariate analysis including ISS stage, age, and time-period of diagnosis. The regions were also evaluated depending on use of modern initial treatment (specific types of drugs, as defined in the study). Region A had the highest use of modern initial treatment and the high usage appeared to correlate to better survival in the ASCT group. We therefore suggest that the superior survival seen in region A possibly depended on differences in treatment between the regions. For the two groups not treated with ASCT (below 75 years and 75 years and older) no clear significant differences in OS were seen after a time to treatment bias was adjusted for in both groups. We speculate that long term effects due to treatment may be harder to show in elderly patients with more comorbidity and death from other causes than myeloma.

In conclusion we have characterized plasma cell disease in Sweden by describing SP, PCL and non-measurable MM including subgroups. We also demonstrate differences in survival between the healthcare regions in Sweden for patients undergoing ASCT and suggest these differences may depend on the usage of initial modern treatment as defined in the study.