Clinical and Population-based Studies in Multiple Myeloma and Monoclonal Gammopathy – Focus on Infections
Year: 2014
Type: dissertation
Abstract: Multiple myeloma is a haematological disorder of the bone marrow. It is preceded by the\nbenign precursor monoclonal gammopathy of undetermined significance (MGUS). In multiple\nmyeloma, a progression leading to expansion of malignant plasma cells occurs, causing\nskeletal lesions, anemia and renal insuffiency. Multiple myeloma is incurable, but the disease\ncan be controlled with chemotherapy and other immunosuppressive drugs. It is known that\nboth conditions have compromised immune responses, which lead to an increased risk of\ninfections. However, there is no population-based data on the occurrence and type of\ninfections in patients with plasma cell disorders compared to the normal population.\nConsidering the cumulative immunodeficiency in patients with multiple myeloma, caused by\nmultiple cytotoxic and immunomodulating therapies, there is a demand for less toxic\ntreatments in the relapse setting, aiming to reduce morbidity and mortality in infections.\nRecent studies have suggested that immunomodulating treatment is beneficial even in\nsmouldering multiple myeloma. There is a lack of population-based incidence data in\nsmouldering multiple myeloma patients with high risk of progressing to multiple myeloma,\nand there is a need of identifying patients with smouldering multiple myeloma that could\nbenefit from up-front treatment.\nIn paper I we investigated the treatment with intermediate-dose melphalan (Mel 100) and\nstem cell support in multiple myeloma patients relapsing after high dose melphalan and\nautologous transplantation (ASCT) in 66 patients. With an overall response of 62%, limited\ntoxicity and a progression-free survival of 8.5 months, we conclude that Mel 100 is a viable\ntherapeutic option in relapsed patients and the best efficacy was seen in patients with longlasting\nresponse after ASCT.\nIn paper II and III we studied the risk of infections in MGUS and multiple myeloma patients\ncompared to matched controls. Using population-based data from Sweden, in paper II we\nestimated the risk of infections among 5 326 MGUS patients compared to 20 161 matched\ncontrols. We found that patients with MGUS had a 2-fold increased increased risk (hazard\nratio (HR) 2.1; 95% confidence interval (CI) 2.0-2.3(p<0.05)) of developing any infection at 5-\nfollow up, and at 10-year follow up the risk was very similar (HR=2.2; 95% CI 2.0-2.3).\nPatients with M-protein concentration over 2.5 mg/dl had the highest risk of infections. In\npaper III we compared the risk of infections in 9 253 multiple myeloma patients to 34 931\nmatched controls. Overall, multiple myeloma patients had a 7-fold (HR =7.1; 95% CI 6.8-7.4)\nrisk of developing any infection compared to matched controls. The increased risk of\ndeveloping a bacterial infection was 7-fold (7.1; 6.8-7.4), and for viral infections it was 10-fold\n(10.0; 8.9-11.4). Multiple myeloma patients diagnosed in the more recent calendar periods had\nsignificantly higher risk of infections compared to patients diagnosed earlier (p<0.001). We\ncould show, that in patients who died within the first year of diagnosis, 22 % of deaths were\ninfection-related. Our findings provide novel insights into the mechanisms behind infections in\npatients with plasma cell disorders, and may have clinical implications and could give support\nto preventive interventions.\nIn paper IV we estimated the risk of progression to symptomatic multiple myeloma in a\ncohort of smouldering multiple myeloma patients with high-risk features using populationbased\ndata from the Swedish Myeloma Registry. The 2-year risk of progressing was 56% and\nthis cohort count for 29% of all smouldering multiple myeloma patients and should be\nconsidered for clinical early treatment trials.
Author: Cecilie Blimark
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2168780290