0000000000280890
AUTHOR
Nikolas Von Bubnoff
Requirements Analysis and Specification for a Molecular Tumor Board Platform Based on cBioPortal
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements …
Updated Results from the German Mpnsg-0212 Combination Trial: Ruxolitinib Plus Pomalidomide in Myelofibrosis with Anemia
Background: Anemia remains one cardinal symptom associated with reduced quality of life (QoL) in patients (pts) with myelofibrosis (MF) which is normally not being addressed by ruxolitinib (RUX). In our previous MPNSG-0109 trial, single-agent pomalidomide (POM) improved cytopenia in 14% (POM 0.5 mg QD) and 29% (POM 2.0 mg QD) of MF pts, respectively. In the MPNSG-0212 study, we sought to investigate the potential synergism of RUX plus POM to improve anemia and QoL in MF pts. Study Design: MPNSG-0212 is an ongoing multicenter, open-label, single-arm phase-Ib/II trial with a target population of 90 pts following a two-stage design (NCT01644110). Pts 1-40 in cohort 1 (co1) were treated with RU…
Genomic Landscape and Molecular Risk in Patients with Advanced Myelofibrosis Treated within the Multicenter Phase Ib/II MPNSG0212 (POMINC) Trial
Abstract Introduction: Mutations (muts) in JAK2, MPL, and CALR are genetic hallmarks in myeloproliferative neoplasms such as myelofibrosis (MF). Prognostication in MF is predominantly based on clinical parameters according to the Dynamic International Prognostic Scoring System (DIPSS). However, gene mutations become increasingly important allowing for a more precised assessment of prognosis. For instance, CALR mutated MF is associated with favorable prognosis, while mutations in distinct high molecular-risk (HMR) genes are considered adverse. Our multicenter phase-Ib/II MPNSG-0212 trial (NCT01644110) investigating ruxolitinib plus pomalidomide in a total cohort of 92 patients with advanced …
Elimination of Established Risk-Factors in Primary Central Nervous System Lymphoma - Impact of High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantaion - a Multicenter Retrospective Analysis
Abstract Abstract 3089 Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in eligible patients (pts). Prognosis of PCNSL is associated with several clinical and histopathological risk factors (RF). Early complete response (CR) during chemotherapy (CHT) was recently reported to be an additional independent prognostic factor in pts undergoing polychemotherapy without HDT+ASCT. In this analysis, we examined the extent to which known RF determined survival in pts who were treated with HDT-ASCT. We additionally investigated the impact of HDT-ASCT specific factors (e…
Validating comprehensive next-generation sequencing results for precision oncology : The NCT/DKTK molecularly aided stratification for tumor eradication research experience
Purpose Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameter…
Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
Abstract The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patient…
Biomarker Analysis in Patients (pts) with Steroid-Refractory Acute Graft-Vs-Host Disease (aGVHD) Treated with Ruxolitinib (RUX) or Best Available Therapy (BAT) in the Randomized, Phase 3 REACH2 Study
BACKGROUND aGVHD, a common complication of allogeneic stem cell transplant (alloSCT), is driven by proinflammatory cytokines and chemokines that activate the immune system, resulting in end-organ damage. Steroids are first-line treatment but up to 50% of pts are steroid refractory (SR), resulting in high mortality and morbidity. RUX, a JAK1/JAK2 inhibitor, inhibits cytokine-dependent activation of the JAK-STAT pathway and cell proliferation and differentiation, which prevents worsening of aGVHD and allows recovery. JAK pathway inhibition by RUX may also lead to modulation of proinflammatory cytokines and prognostic GVHD biomarkers. The phase 3 randomized REACH2 trial (NCT02913261) in SR aGV…
Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation
High-dose chemotherapy followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed primary central nervous system lymphoma. In this retrospective multicenter study, we investigated prognosis and baseline risk factors in patients with primary central nervous system lymphoma who underwent this treatment approach. We retrospectively analyzed 105 immunocompetent patients with primary central nervous system lymphoma who underwent high-dose chemotherapy followed by autologous stem cell transplantation with or without whole brain radiotherapy as first-line consolidation treated at 12 German centers between 1997 and 2011. We estimated survi…
Ruxolitinib Plus Pomalidomide in Myelofibrosis: Updated Results from the Mpnsg-0212 Trial (NCT01644110)
Abstract Background: Although ruxolitinib (RUX) reduces constitutional symptoms and splenomegaly in myelofibrosis (MF) therapy options for anemia are limited. In our prior MPNSG-0109 trial of pomalidomide (POM) in MF with cytopenia, anemia responses were reported in 14% and 29% of subjects receiving POM 0.5 mg/d and 2 mg/d, respectively (Schlenk RF et al., ASH 2013, abstract #2822). We designed a phase-Ib/-II combination study of RUX plus POM to evaluate synergistic effects in subjects with anemia and splenomegaly (MPNSG-0212 trial, NCT01644110; Stegelmann et al., ASH 2015, abstract #826). Study Design: Primary endpoints are response rate after 12 treatment cycles (28 days each) according t…