12 results on '"Borchmann, Sven"'
Search Results
2. Novel agents in classical Hodgkin lymphoma.
- Author
-
Borchmann, Sven and von Tresckow, Bastian
- Subjects
- *
HODGKIN'S disease , *HODGKIN'S disease treatment , *IMMUNOGLOBULINS , *OLDER patients , *DRUG efficacy , *PATIENTS , *DISEASES - Abstract
Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches. This review aims to give a comprehensive overview of novel agents in Hodgkin lymphoma that have been recently or are currently being evaluated in clinical trials. In addition to dedicated sections on brentuximab vedotin (BV) and immune checkpoint inhibitors, other emerging substances and concepts are discussed. In doing so, this review compares trial results regarding safety and efficacy. A special focus lies on the effect novel agents will have on the different treatment settings faced by clinicians involved in the treatment of Hodgkin lymphoma. [ABSTRACT FROM PUBLISHER]
- Published
- 2017
- Full Text
- View/download PDF
3. Multi-Specific Antibodies for Cancer Immunotherapy.
- Author
-
Jachimowicz, Ron, Borchmann, Sven, and Rothe, Achim
- Subjects
- *
CANCER treatment , *CANCER immunotherapy , *THERAPEUTIC use of monoclonal antibodies , *ANTINEOPLASTIC agents , *HEALTH outcome assessment , *CLINICAL trials , *PRIMARY care - Abstract
Targeted treatment of cancer with monoclonal antibodies has added to the beneficial outcome of patients. In an attempt to improve anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research arena. To date, only a few multi-specific constructs have entered phase III clinical trials, in contrast to classical monoclonal antibodies, which are the standard first-line therapy in several tumor entities. In this review, we will assess selected multi-specific antibodies in pre-clinical and clinical development that may be new treatment options for cancer patients in the very near future. We will further evaluate therapy modalities including the timely distribution or the combination of various therapeutic approaches and assess the potential role of multi-specific antibodies in cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
4. Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients.
- Author
-
Momotow, Jesko, Borchmann, Sven, Eichenauer, Dennis A., Engert, Andreas, Sasse, Stephanie, and Huebel, Kai
- Subjects
- *
HODGKIN'S disease , *STEM cell transplantation , *INCURABLE diseases , *PROGNOSIS , *COMBINED modality therapy - Abstract
Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Noninvasive minimal residual disease assessment in relapsed/refractory large B‐cell lymphoma using digital droplet PCR.
- Author
-
Heger, Jan‐Michel, d'Hargues, Yannick, Kleinert, Fanni, Mattlener, Julia, Weiss, Jonathan, Franzen, Fabian, Becker, Christian, Becker, Kerstin, Gödel, Philipp, Schmiel, Marcel, Meinel, Jörn, Flümann, Ruth, Simon, Florian, Reinhardt, H. Christian, Borchmann, Peter, Borchmann, Sven, Balke‐Want, Hyatt, Knittel, Gero, and von Tresckow, Bastian
- Subjects
- *
DIFFUSE large B-cell lymphomas , *LYMPHOMAS , *DNA sequencing - Abstract
Although several promising approaches for the treatment of relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long‐term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost‐ and time‐sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof‐of‐principle for its ability to predict outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO).
- Author
-
Gillessen, Sarah, Pluetschow, Annette, Vucinic, Vladan, Ostermann, Helmut, Kobe, Carsten, Bröckelmann, Paul J., Böll, Boris, Eichenauer, Dennis A., Heger, Jan‐Michel, Borchmann, Sven, Fuchs, Michael, Borchmann, Peter, Engert, Andreas, and von Tresckow, Bastian
- Subjects
- *
HODGKIN'S disease , *RUXOLITINIB , *CLINICAL trials , *OVERALL survival , *DISEASE progression - Abstract
Objectives: Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods: Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989). Results: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. EGFR Inhibition Strongly Modulates the Tumour Immune Microenvironment in EGFR-Driven Non-Small-Cell Lung Cancer.
- Author
-
Selenz, Carolin, Compes, Anik, Nill, Marieke, Borchmann, Sven, Odenthal, Margarete, Florin, Alexandra, Brägelmann, Johannes, Büttner, Reinhard, Meder, Lydia, and Ullrich, Roland T.
- Subjects
- *
LUNG cancer , *BIOLOGICAL models , *IMMUNE checkpoint inhibitors , *EPIDERMAL growth factor receptors , *ANIMAL experimentation , *ANTINEOPLASTIC agents , *ERLOTINIB , *REGULATORY T cells , *CELLULAR signal transduction , *CELL proliferation , *CELL lines , *TRANSGENIC animals , *IMMUNOTHERAPY , *MICE , *DRUG resistance in cancer cells , *PHARMACODYNAMICS - Abstract
Simple Summary: Lung cancer that is driven by mutations in the epidermal growth factor receptor (EGFR) is currently treated with tyrosine kinase inhibitors (TKIs). Although patients initially respond well to TKI treatment, drug resistance against EGFR-targeted therapy emerges. Attempts to combine immunotherapy with EGFR-targeted treatment to prolong response rates or prevent the development of resistances have been limited due to insufficient knowledge about the effects of targeted therapy on the tumour microenvironment (TME) in EGFR-driven tumours and tumour-infiltrating immune cells. The aims of this study were to improve our understanding on the impact of EGFR inhibition on the immune response in EGFR-driven lung cancer and, furthermore, to gain insights into the impact of combining targeted therapy with immunotherapy on the TME. EGFR-driven non-small-cell lung cancer (NSCLC) patients are currently treated with TKIs targeting EGFR, such as erlotinib or osimertinib. Despite a promising initial response to TKI treatment, most patients gain resistance to oncogene-targeted therapy, and tumours progress. With the development of inhibitors against immune checkpoints, such as PD-1, that mediate an immunosuppressive microenvironment, immunotherapy approaches attempt to restore a proinflammatory immune response in tumours. However, this strategy has shown only limited benefits in EGFR-driven NSCLC. Approaches combining EGFR inhibition with immunotherapy to stimulate the immune response and overcome resistance to therapy have been limited due to insufficient understanding about the effect of EGFR-targeting treatment on the immune cells in the TME. Here, we investigate the impact of EGFR inhibition by erlotinib on the TME and its effect on the antitumour response of the immune cell infiltrate. For this purpose, we used a transgenic conditional mouse model to study the immunological profile in EGFR-driven NSCLC tumours. We found that EGFR inhibition mediated a higher infiltration of immune cells and increased local proliferation of T-cells in the tumours. Moreover, inhibiting EGFR signalling led to increased activation of immune cells in the TME. Most strikingly, combined simultaneous blockade of EGFR and anti-PD-1 (aPD-1) enhanced tumour treatment response in a transgenic mouse model of EGFR-driven NSCLC. Thus, our findings show that EGFR inhibition promotes an active and proinflammatory immune cell infiltrate in the TME while improving response to immune checkpoint inhibitors in EGFR-driven NSCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Reinduction therapy with everolimus in combination with dexamethasone, high‐dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD‐R3i)
- Author
-
Gillessen, Sarah, Hüttmann, Andreas, Vucinic, Vladan, Müller, Horst, Plütschow, Annette, Viardot, Andreas, Topp, Max S., Kobe, Carsten, Böll, Boris, Eichenauer, Dennis A., Sasse, Stephanie, Haverkamp, Heinz, Schmitz, Christine, Borchmann, Sven, Bröckelmann, Paul J., Heger, Jan‐Michel, Fuchs, Michael, Engert, Andreas, Borchmann, Peter, and von Tresckow, Bastian
- Subjects
- *
HODGKIN'S disease , *EVEROLIMUS , *STEM cell transplantation , *DEXAMETHASONE , *COMPUTED tomography - Abstract
Summary: Reinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial.
- Author
-
Gerhard‐Hartmann, Elena, Goergen, Helen, Bröckelmann, Paul J., Mottok, Anja, Steinmüller, Tabea, Grund, Johanna, Zamò, Alberto, Ben‐Neriah, Susana, Sasse, Stephanie, Borchmann, Sven, Fuchs, Michael, Borchmann, Peter, Reinke, Sarah, Engert, Andreas, Veldman, Johanna, Diepstra, Arjan, Klapper, Wolfram, and Rosenwald, Andreas
- Subjects
- *
PROGRAMMED death-ligand 1 , *HODGKIN'S disease , *MANTLE cell lymphoma , *MAJOR histocompatibility complex - Abstract
Summary: High programmed cell death 1 ligand 1 (PD‐L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin‐ and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti‐PD‐1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD‐L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti‐PD‐1‐based first‐line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced‐stage or r/r cHL. All but two cases (97%) showed PD‐L1 expression by the tumour cells in variable amounts. While MHC‐I was rarely expressed in >50% of HRSC, MHC‐II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD‐L1 and MHC‐I/II expression on early response to the highly effective anti‐PD‐1‐based NIVAHL first‐line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti‐PD‐1 first‐line cHL treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. The translational science of hodgkin lymphoma.
- Author
-
Cirillo, Melita, Reinke, Sarah, Klapper, Wolfram, and Borchmann, Sven
- Subjects
- *
HODGKIN'S disease , *TRANSLATIONAL research , *FIBROSIS , *JAK-STAT pathway , *CANCER cells , *GENOMICS - Abstract
Summary: Hodgkin Lymphoma (HL) is an unusual B‐cell lymphoma because the malignant cells exist as a minority population in a densely cellular microenvironment. The microenvironment is comprised predominately of inflammatory and immune cells with fibrosis in some cases. There are multiple dysregulated signalling pathways that sustain HL within this microenvironment, such as the Nuclear factor‐κB and Janus kinase/signal transducers and activators of transcription pathways. Advances in genomic medicine have enabled a better characterisation of the rare tumour cells and improved our understanding of the signalling mechanisms that exist between the malignant cell and its microenvironment. Current therapy for HL produces excellent clinical outcomes in most younger patients. However, problems with current treatment approaches include poorer outcomes in the elderly, toxicity of highly‐effective combination chemotherapy regimens and relapse in high‐risk patients. Better understanding of disease biology aids in upfront prognostication of patients, defines new methods for treatment monitoring and assists in the recognition of novel targets for therapy. Biology‐driven therapies, including anti‐CD30 antibody conjugates, cellular immunotherapies and immune modulation, particularly with checkpoint inhibitors, have changed treatment algorithms for relapsed/refractory patients. Future challenges exist in incorporating immune‐based therapies earlier in treatment algorithms to reduce toxicity and prevent relapse for patients with HL. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
11. Leucocyte and eosinophil counts predict progression‐free survival in relapsed or refractory classical Hodgkin Lymphoma patients treated with PD1 inhibition.
- Author
-
Hude, Ida, Sasse, Stephanie, Bröckelmann, Paul J., von Tresckow, Bastian, Momotow, Jesko, Engert, Andreas, and Borchmann, Sven
- Subjects
- *
PROGRESSION-free survival , *HODGKIN'S disease , *EOSINOPHILS , *LEUCOCYTES , *IMMUNE response - Abstract
The article provides information on a study which observed the link between different blood count parameters at baseline with response and progression-free survival (PFS) in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL) patients treated with the anti-PD1 antibody, nivolumab. Topics discussed include role of eosinophils as co-effectors of the immune response, and results of the study.
- Published
- 2018
- Full Text
- View/download PDF
12. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials.
- Author
-
Böll, Boris, Goergen, Helen, Behringer, Karolin, Bröckelmann, Paul J., Hitz, Felicitas, Kerkhoff, Andrea, Greil, Richard, von Tresckow, Bastian, Eichenauer, Dennis A., Bürkle, Carolin, Borchmann, Sven, Fuchs, Michael, Diehl, Volker, Engert, Andreas, and Borchmann, Peter
- Subjects
- *
BLEOMYCIN , *HODGKIN'S disease , *RADIOTHERAPY , *RANDOMIZED controlled trials , *CANCER chemotherapy , *PATIENTS - Abstract
Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients ≥60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2 x ABVD; n = 137) or AVD (23AVD; n= 82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 43ABVD1IFRT (n568). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 23AVD and 2 x ABVD (40% and 39%, respectively), but considerably higher in patients receiving 43ABVD (65%). Similarly, BLT was rare in patients receiving 2 x ABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 43ABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13). [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.