A real-world study on the impact of infection load on mortality in multiple myeloma patients in Finland.

Infections are a clinically significant cause of mortality in multiple myeloma (MM) patients. The high number of infections in MM patients is due to the immunosuppressive effects of the disease itself as well as treatment-related immunosuppression. In this real-world evidence (RWE) study, we used several nationwide healthcare registries of Finland to investigate the effect of infection load on mortality in MM patients during 1997-2021.

Comorbidities and survival of multiple myeloma patients diagnosed in Finland between 2000 and 2021.

Advances in treatment have improved the survival of multiple myeloma (MM) patients, but the disease remains incurable. Here, in this nationwide retrospective real-world evidence (RWE) study, we report the patient characteristics, incidence, overall survival outcomes, comorbidities, and healthcare resource utilization (HCRU) of all adult MM patients diagnosed between 2000 and 2021 in Finland. A total of 7070 MM patients and their 21,210 age-, sex- and region-matched controls were included in the analysis.

Ixazomib, Lenalidomide, and Dexamethasone (IRD) Treatment with Cytogenetic Risk-Based Maintenance in Transplant-Eligible Myeloma: A Phase 2 Multicenter Study by the Nordic Myeloma Study Group.

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib-lenalidomide-dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients.

Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation.

Background: Multiple myeloma is currently the leading indication for autologous hematopoietic cell transplantation (AHCT). A prerequisite for AHCT is mobilization and collection of adequate blood graft to support high-dose therapy. Current mobilization strategies include granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy most commonly cyclophosphamide (CY).

Real-world evidence of multiple myeloma treated from 2013 to 2019 in the Hospital District of Helsinki and Uusimaa, Finland.

The rapid development of multiple myeloma (MM) management underscores the value of real-world data. In our study we examined 509 adult MM patients treated with immunochemotherapy (ICT) with/without stem cell transplantation (SCT) from 2013 to 2019 in the Hospital District of Helsinki and Uusimaa, Finland. Our study was based on computational analyses of data integrated into the hospital data lake.

Deep Immune Profiling of Multiple Myeloma at Diagnosis and under Lenalidomide Maintenance Therapy.

The bone marrow microenvironment interacts with malignant cells and regulates cancer survival and immune evasion in multiple myeloma (MM). We investigated the immune profiles of longitudinal bone marrow samples from patients with newly diagnosed MM ( = 18) using cytometry by time-of-flight. The results before and during treatment were compared between patients with good (GR, = 11) and bad (BR, = 7) responses to lenalidomide/bortezomib/dexamethasone-based treatment.

A germline exome analysis reveals harmful variants in multiple myeloma patients and families.

Observations of inherited susceptibility to multiple myeloma have led to active research in defining predisposing genes to the disease. Here, we analysed 128 plasma cell dyscrasia patients' germline whole-exome sequencing data. Rare dominantly inherited pathogenic or likely pathogenic (P/LP) variant was found in 9.

Impact of the number of cryopreserved CD34 cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

Background: Prospective data on the impact of CD34 cell loss during cryopreservation and the amount of cryopreserved CD34 cells infused after high-dose therapy on hematologic recovery and post-transplant outcome in multiple myeloma (MM) are scarce.

Patients And Methods: This post-hoc study aimed to investigate factors associating with CD34 cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 10 /kg, group A), low number (1-1.

Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group.

Objectives: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy.

Methods: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification.

Comparison of CD34 cell mobilization, blood graft cellular composition, and post-transplant outcome in myeloma patients mobilized with filgrastim or pegfilgrastim added to low-dose cyclophosphamide: A prospective multicenter study.

Background: Scarce data exist on the impact of granulocyte-colony stimulating factor (G-CSF) type on the mobilizing capacity of CD34 cells, graft cellular composition, and outcome in myeloma (MM) patients.

Patients And Methods: In this prospective multicenter study, 70 patients with MM received filgrastim (FIL) and 20 patients received pegfilgrastim (PEG) as a G-CSF after low-dose cyclophosphamide. Flow cytometry was used to analyze the mobilization of CD34 cells and cellular composition of blood grafts, hematologic recovery, and survival after auto-SCT according to the G-CSF choice.

S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma.

Despite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM.

Next generation proteomics with drug sensitivity screening identifies sub-clones informing therapeutic and drug development strategies for multiple myeloma patients.

With the introduction of novel therapeutic agents, survival in Multiple Myeloma (MM) has increased in recent years. However, drug-resistant clones inevitably arise and lead to disease progression and death. The current International Myeloma Working Group response criteria are broad and make it difficult to clearly designate resistant and responsive patients thereby hampering proteo-genomic analysis for informative biomarkers for sensitivity.

Autograft cellular composition and outcome in myeloma patients: Results of the prospective multicenter GOA study.

Background: Autologous stem cell transplantation (auto-SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known.

Study Design And Methods: Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study.

Long-term outcome after allogeneic stem cell transplantation in multiple myeloma.

The role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000-2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse.

Prognostic significance of esterase gene expression in multiple myeloma.

Background: Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM).

Methods: For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM).

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non-Hodgkin's lymphoma patients: results of the prospective multicenter GOA study.

Background: Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).

Study Design And Methods: In this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome.

Results: Multiple myeloma patients mobilized CD34+ cells more effectively (6.

RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group.

Autologous stem cell transplantation (ASCT) combined with novel agents is the standard treatment for transplant-eligible, newly diagnosed myeloma (NDMM) patients. Lenalidomide is approved for maintenance after ASCT until progression, although the optimal duration of maintenance is unknown. In this trial, 80 patients with NDMM received three cycles of lenalidomide, bortezomib, and dexamethasone followed by ASCT and lenalidomide maintenance until progression or toxicity.

Real-world treatment outcomes in multiple myeloma: Multicenter registry results from Finland 2009-2013.

Unlabelled: Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data.

Blood graft composition and post-transplant recovery in myeloma patients mobilized with plerixafor: a prospective multicenter study.

The composition of autologous blood grafts after cryopreservation, post-transplant hematological recovery up to 1 year and immune recovery up to 6 months as well as outcome was analyzed in 87 patients with multiple myeloma (MM). The patients receiving added plerixafor due to poor mobilization (11%) were compared to those mobilized with G-CSF or cyclophosphamide (CY) plus G-CSF. The use of plerixafor was found to significantly affect the graft composition as there was a significantly higher proportion of the more primitive CD34 cells, higher number of T and B lymphocytes as well as NK cells in the grafts of patients who received also plerixafor.

Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated drug sensitivity to patient outcome.