Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.

Purpose: Survival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities.

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

Rationale And Objectives: To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies.

Materials And Methods: The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial.

Previously, addition of isatuximab (Isa) to standard-of-care lenalidomide-bortezomib-dexamethasone (RVd) in transplant-eligible patients with newly diagnosed multiple myeloma in the GMMG-HD7 trial (ClinicalTrials.gov identifier: NCT03617731) resulted in a significant increase of minimal residual disease negativity (MRD-) rates after induction therapy. A total of 662 patients were randomly assigned to receive induction therapy with Isa-RVd (n = 331) or RVd (n = 329), followed by single or tandem autologous stem-cell transplant and second random assignment to maintenance with lenalidomide alone or Isa-lenalidomide.

Mutagenic impact and evolutionary influence of radiotherapy in hematologic malignancies.

Ionizing radiotherapy (RT) is a widely used palliative and curative treatment strategy for malignancies. In solid tumors, RT-induced double strand breaks lead to the accumulation of indels, and their repair by non-homologous end-joining has been linked to the ID8 mutational signature in resistant cells. However, the extent of RT-induced DNA damage in hematologic malignancies and its impact on their evolution and interplay with commonly used chemotherapies has not yet been explored.

EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell-associated hematotoxicity (ICAHT), predisposing for life-threatening infections.

Methods: This retrospective observational study examined a total of 129 patients with RRMM who had received idecabtagene vicleucel (ide-cel) at two major myeloma centers in Germany and one center in the USA to assess the Endothelial Activation and Stress Index (EASIX) as a risk marker for an unfavorable clinical course and outcome after CAR T-cell therapy.

Longitudinal assessment of established risk stratification models in patients with monoclonal gammopathy of undetermined significance.

Risk of progression of monoclonal gammopathy of undetermined significance (MGUS) into multiple myeloma and related plasma cell disorders can be determined by three major risk stratification models, namely Mayo2005, Sweden2014, and NCI2019. This retrospective study of 427 patients with MGUS diagnosed according to the 2014 International Myeloma Working Group criteria aimed to describe and analyze the longitudinal applicability of these risk models. In all three models, the majority of patients remained at their baseline risk group, whereas small numbers of patients migrated to a different risk group.

Reproducible Radiomics Features from Multi-MRI-Scanner Test-Retest-Study: Influence on Performance and Generalizability of Models.

Background: Radiomics models trained on data from one center typically show a decline of performance when applied to data from external centers, hindering their introduction into large-scale clinical practice. Current expert recommendations suggest to use only reproducible radiomics features isolated by multiscanner test-retest experiments, which might help to overcome the problem of limited generalizability to external data.

Purpose: To evaluate the influence of using only a subset of robust radiomics features, defined in a prior in vivo multi-MRI-scanner test-retest-study, on the performance and generalizability of radiomics models.

The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma.

Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.

Artificial intelligence-based, volumetric assessment of the bone marrow metabolic activity in [F]FDG PET/CT predicts survival in multiple myeloma.

Purpose: Multiple myeloma (MM) is a highly heterogeneous disease with wide variations in patient outcome. [F]FDG PET/CT can provide prognostic information in MM, but it is hampered by issues regarding standardization of scan interpretation. Our group has recently demonstrated the feasibility of automated, volumetric assessment of bone marrow (BM) metabolic activity on PET/CT using a novel artificial intelligence (AI)-based tool.

Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial.

Objectives: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown.

Methods: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months.

Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial.

Background: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma.

Methods: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups.

The impact of divergent forms of social support on health-related quality of life in patients with multiple myeloma and its precursor states.

Purpose: Multiple myeloma is a largely incurable disease. Patients suffer from the cancer, therapeutic side effects, and often psychological symptoms. Not only multiple myeloma patients but also patients with precursor diseases show high psychological distress.

Sequence diversity of kappa light chains from patients with AL amyloidosis and multiple myeloma.

Background: AL amyloidosis (AL) results from the misfolding of immunoglobulin light chains (IG LCs). Aim of this study was to comprehensively analyse kappa LC sequences from AL patients in comparison with multiple myeloma (MM).

Objective: We analysed usage and associated organ tropism and in terms of mutational analysis and theoretical biochemical properties.

Genomic Classification and Individualized Prognosis in Multiple Myeloma.

Purpose: Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years.

Methods: To decipher and predict the molecular and clinical heterogeneity of NDMM, we assembled a series of 1,933 patients with available clinical, genomic, and therapeutic data.

Results: Leveraging a comprehensive catalog of genomic drivers, we identified 12 groups, expanding on previous gene expression-based molecular classifications.

Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients.

Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005-2020 with novel agent-based triplet/quadruplet IT.

Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials.

Background: While quadruplet induction therapies deepen responses in newly diagnosed multiple myeloma patients, their impact on peripheral blood stem cell (PBSC) collection remains incompletely understood. This analysis aims to evaluate the effects of prolonged lenalidomide induction and isatuximab- or elotuzumab-containing quadruplet induction therapies on PBSC mobilization and collection.

Methods: A total of 179 transplant-eligible patients with newly diagnosed MM treated at a single academic center were included.

Health-Related Quality of Life in Multiple Myeloma Patients Treated with High- or Low-Dose Lenalidomide Maintenance Therapy after Autologous Stem Cell Transplantation-Results from the LenaMain Trial (NCT00891384).

Introduction: The LenaMain trial (NCT00891384) reported increased progression-free survival with 25 mg of lenalidomide maintenance compared to 5 mg. Here, we report the patient-reported outcomes.

Materials And Methods: Scores obtained from the EORTC Quality of Life Questionnaire C30 were analyzed for longitudinal changes from baseline within the groups as well as cross-sectional scores.