Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM.

Effectiveness of high efficiency particulate (HEPA) air condition combined with the antifungal prophylaxis on incidence, morbidity and mortality of invasive fungal infections in patients with acute myeloid leukemia: a retrospective single-center study.

Introduction: Our monocentric and retrospective study aimed to investigate the clinical effectivity of HEPA filters in combination with the antifungal drug prophylaxis in patients with AML undergoing intensive chemotherapy and allogeneic stem cell transplantation (SCT).

Methods/results: We included 177 patients between 2005 and 2015 representing a total of 372 in-hospital stays, 179 in the HEPA cohort (+HEPA) and 193 in the cohort without HEPA filters (-HEPA). No significant additional benefit of HEPA filtration on the risk reduction of IFI was observed.

A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma.

MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen.

Transcriptome Profiling Associated with Overexpression in Colorectal Cancer Implicates a Potential Role for Tumor Immune Microenvironment and Cancer Pathways Modulation via NF-κB.

The immune system plays a critical role in inflammation by initiating responses to infections or tissue damage. The nuclear factor-κB (NF-κB) pathway plays a key role in inflammation and innate immunity, as well as other cellular activities. Dysregulation of this well-choreographed pathway has been implicated in various diseases, including cancer.

The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.

Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies.

A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation.

Introduction: In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34 precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g.

Mobilization and Hematopoietic Stem Cell Collection in Poor Mobilizing Patients with Lymphoma: Final Results of the German OPTIMOB Study.

Introduction: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome.

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial.

Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI.

Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy.

Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10% to 15% among patients with acute myeloid leukemia (AML) and 5% to 7% among healthy Caucasians and promotes the development of this disease.

Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma.

Background: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.

Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells.

Growth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose-dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose-dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells.

Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma-A Critical Toxicity Evaluation in the Modern Treatment Era.

Radiotherapy (RT) is an established treatment modality in the management of patients with multiple myeloma (MM), aiming at analgesia and stabilization of osteolytic lesions. As a multifocal disease, the combined use of RT, systemic chemotherapy, and targeted therapy (ST) is pivotal to achieve better disease control. However, adding RT to ST may lead to increased toxicity.

Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma.

Multiple myeloma (MM) is an incurable, malignant B cell disorder characterized by frequent relapses and a poor prognosis. Thus, new therapeutic approaches are warranted. The phosphatidylinositol-3-kinase (PI3K) pathway plays a key role in many critical cellular processes, including cell proliferation and survival.

The RNA helicase DDX3 and its role in c-MYC driven germinal center-derived B-cell lymphoma.

DDX3X is an RNA helicase with many functions in RNA metabolism such as mRNA translation, alternative pre-mRNA splicing and mRNA stability, but also plays a role as a regulator of transcription as well as in the Wnt/beta-catenin- and Nf-κB signaling pathways. The gene encoding DDX3X is located on the X-chromosome, but escapes X-inactivation. Hence females have two active copies and males only one.

A phase 2 clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma.

Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily.

Electrostatic anti-CD33-antibody-protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in myeloid progenitor cells, with a worldwide 5-year survival prognosis of about 30%. Therefore, the development of more effective therapeutics with novel mode of action is urgently demanded. One common mutated gene in the AML is the DNA-methyltransferase DNMT3A whose function in the development and maintenance of AML is still unclear.

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario.

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines.

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial.

Background: Anti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.

Methods: This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany.

Presence of the single nucleotide polymorphism enhances the response of leukemic cells to CDK4/6 inhibition.

The zinc finger protein Growth Factor Independence 1 (GFI1) acts as a transcriptional repressor regulating differentiation of myeloid and lymphoid cells. A single nucleotide polymorphism of , , has a prevalence of 7% in healthy Caucasians and 15% in acute myeloid leukemia (AML) patients, hence most probably predisposing to AML. One reason for this is that GFI1-36N differs from the wildtype form GFI1-36S regarding its ability to induce epigenetic changes resulting in a derepression of oncogenes.

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers.