Nicola Giesen

The Infectious Diseases Working Party (AGIHO) was established in 1996 as one of the subgroups of the German Society of Hematology and Medical Oncology (DGHO). Marking its 30th anniversary this year, the AGIHO reflects on a period of significant achievement and growth. Beyond its core mission of developing evidence-based clinical practice guidelines for the prevention, diagnosis, and management of infections in patients with cancer, the AGIHO has evolved into a vital platform for clinical trials, collaborative research, and postgraduate medical education. To ensure long-term sustainability and foster emerging talent, “Young AGIHO” was launched in 2023. This initiative aims to strengthen networking among early career physicians specializing in hematology and oncology with a strong focus on infectious diseases. The working party has also expanded its geographical footprint by integrating colleagues from Austria and Switzerland, thereby enhancing its international presence. Through the publication of guidelines in high-ranking international journals, AGIHO visibility has increased significantly. Representatives of the working party now serve as experts for scientific and health policy committees both nationally and internationally. As one of the DGHO's largest and most active subgroups, the AGIHO is ideally positioned to address future challenges in the field.

Purpose In patients with hematological malignancies and central venous catheters (CVC) men have a higher risk for CVC related bloodstream infections (CRBSI) than women. Hence, preventive strategies such as earlier CVC removal may reduce the overall CRBSI (oCRBSI) rate. Methods A randomized simulation using data from a CVC registry was performed. Data were derived from unselected patients with hematological or oncological diseases and a CVC. Patients were randomized to an experimental (EXP-G) or control group (CON-G). For the men in the EXP-G, one-day increments of an earlier CVC removal were simulated based on actual data and compared to men in the CON-G without simulation. The primary endpoint was oCRBSI rate. Results Underlying diseases were mainly hematological malignancies (87.3%). In the male patients with a median CVC in situ time of 13 days, the oCRBSI rate was 7.3% (103/1408), with 7.3% (53/729) in the EXP-G and 7.4% (50/679) in the CON-G. In the EXP-G, simulated shortening of CVC time by 1 day in men resulted in an oCRBSI rate of 5.2% compared with 7.4% in the CON-G ( p = 0.12). Shortening CVC time by 2 days led to an oCRBSI rate of 4% ( p = 0.008); the corresponding median CVC time was 11 days. A 3-day shortening further to 10 days reduced the oCRBSI rate to 2.7% ( p < 0.001). Women from the same registry showed a 3.3% (30/920) oCRBSI rate after 12 days. Conclusion In conclusion, shortening the CVC dwell time in men by 2 or 3 days, corresponding to a CVC duration of 10–11 days, reduces the CRBSI rate in men and mitigates the higher risk, compared to women. Clinical Trial Registration: SECRECY (Study to Evaluate Central Venous Catheter-related Infections in Hematology and Oncology) was registered within the German Clinical Trial Register (DRKS; no. DRKS00006551) on 29 September 2014.

Introduction: Men are generally more susceptible to bacterial infections than women. Central venous catheters (CVCs), often used to administer systemic treatment in patients with cancer, are an important source of infection. However, little is known about sex-specific differences of CVC-related bloodstream infections (CRBSIs) in patients with cancer. This study aimed to compare CRBSIs in men versus women in a large cohort of patients with cancer. Methods: Data were derived from the SECRECY registry including nonselected patients with centrally inserted non-tunneled internal jugular or subclavian vein CVCs in 10 hematology and oncology sites in Germany. Only CRBSIs classified as definite CRBSI (dCRBSI) or probable CRBSI were included, and the combination of both was summarized as dpCRBSI. CVCs were matched 1:1 for underlying disease, anatomic site of CVC insertion, type of CVC dressing, antimicrobial coated CVC, complicated CVC insertion, and CVC in situ time by propensity score matching (PSM). Endpoints were CRBSI rates and incidences in CVCs inserted in men versus women. Results: A total of 5,075 CVCs registered from March 2013 to March 2024 were included in the analysis, of which 3,024 comprise the PSM cohort. A total of 1,512 (50.0%) CVCs were inserted in men. Underlying diseases mainly were hematological malignancies (96.4%). While there was no statistically significant difference between men and women in the dCRBSI rate (5.4% vs. 4.1%; p = 0.12) and the dCRBSI incidence (3.8 vs. 2.9/1,000 CVC days; p = 0.11), the rate of dpCRBSI (9.9% vs. 6.7%; p = 0.002) and the dpCRBSI incidence (7.0 vs. 4.7/1,000 CVC days; p = 0.002) were significantly higher in men versus women. The proportion of coagulase-negative staphylococci as causative agent of both dCRBSI and dpCRBSI was higher in men than in women (58.8% vs. 41.2%; p = 0.07 and 61.5% vs. 38.5%; p = 0.002, respectively). A multivariable regression revealed neutropenia as an independent risk factor for dCRBSI and male sex as risk factor for dCRBSI and dpCRBSI. Conclusion: In patients with hematological malignancies, men have a higher risk of CRBSI than women. This finding may be attributed to the high number of jugular vein-inserted CVCs, which in men may be associated with higher rates of skin colonization than in women. Special preventive measures such as earlier removal of CVCs in men may be studied in future.

Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma. We assess transcriptomic and epigenomic changes to resolve the multifactorial nature of therapy resistance and relate it to the parallel occurrence of different mechanisms: (1) preexisting epigenetic profiles of subclones associated with survival advantages, (2) converging phenotypic adaptation of genetically distinct subclones, and (3) subclone-specific interactions of myeloma and bone marrow microenvironment cells. Our study showcases how an integrative multiomics analysis can be applied to track and characterize distinct multidrug-resistant subclones over time for the identification of molecular targets against them.

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. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10 patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.

Patients with cancer are at particular risk for infection but also have diminished vaccine responses, usually quantified by the level of specific antibodies. Nonetheless, vaccines are specifically recommended in this vulnerable patient group. Here, we discuss the cellular part of the vaccine response in patients with cancer. We summarize the experience with vaccines prior to and during the SARS-CoV-2 pandemic in different subgroups, and we discuss why, especially in patients with cancer, T cells may be the more reliable correlate of protection. Finally, we provide a brief outlook on options to improve the cellular response to vaccines.

The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. In this study, we performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity; the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients; a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.