Search

Objective: We describe real-world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). Method: First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005–2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. Results: We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high-risk MM in a real- world-population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. Conclusion: National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.

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 subgr

Objective: We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Methods: Oligo-secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio. Results: Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7 months, non-measurable MM 40.2 months, oligo-secretory MM 38.6 months, and non-secretory MM 44.6 months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015). Conclusion: In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease.

Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.