Publications by authors named "Jonathan Brammer"

Article Synopsis
  • Researchers are testing valemetostat, an EZH2 and EZH1 inhibitor, for safety and effectiveness in patients with relapsed or refractory non-Hodgkin lymphoma, due to limited treatment options and poor outcomes.
  • The study involved 90 participants from 19 hospitals across Japan and the USA, who received varying doses of valemetostat in a phase 1 clinical trial to find the right dosage and assess its anti-tumor effects.
  • Initial findings will help determine the most effective dosages and provide insights into the drug's safety profile, with a majority of patients having peripheral T-cell lymphoma.
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  • Post-stem cell transplant (SCT) maintenance therapy is being explored as a way to improve outcomes for patients with peripheral T-cell lymphomas (PTCL), as relapse after SCT is common.
  • Recent studies of agents like romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab show promise in reducing relapse rates post-SCT.
  • Ongoing trials continue to evaluate the effectiveness of these maintenance therapies, suggesting that they could be a significant strategy in managing PTCL.
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  • FDA-approved treatments ruxolitinib and belumosudil are effective as steroid-sparing agents for chronic GVHD with overall response rates of 76% and 65% respectively.
  • A study of 20 patients using a combination of these agents showed a 55% overall response rate, helping patients reduce or stop other immunosuppressants without major complications.
  • The combination therapy proved tolerable, did not worsen blood cell counts, and successfully postponed the need for more aggressive treatments.
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Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach.

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  • - The study examined gender representation in clinical trials for FDA-approved anticancer drugs from 1998-2018, focusing on participation rates of women compared to men across various cancer types.
  • - Findings indicated that women constituted only 40.7% of participants in 148 trials, with significant under-representation in trials for gastric, liver, and lung cancers, while sex-specific efficacy and safety data were rarely reported (only 4% of trials).
  • - Despite low female enrollment, there was no correlation between the percentage of women recruited and drug efficacy, highlighting a persistent gap in gender representation in cancer research.
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Background: CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes.

Methods: We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP-BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada.

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  • Hematopoietic stem cell transplantation (HSCT) can treat various serious blood disorders but increases the risk of cardiovascular issues, particularly for patients undergoing allogeneic transplantation compared to autologous.
  • A study analyzed data from the National Inpatient Sample (2016-2019) to compare the rates of atrial fibrillation (AF) and major adverse cardiac events (MACE) between the two transplantation types.
  • Findings revealed that allogeneic HSCT patients have significantly higher odds of experiencing serious heart problems and mortality during hospitalization, with AF being a key predictor of poor outcomes.
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  • * A study analyzed data from patients treated with auto-HCT (281 patients) and CAR-T (79 patients) between 2015 and 2021, revealing that auto-HCT had a higher 2-year progression-free survival (66.2% vs. 47.8%) and lower relapse rate (27.8% vs. 48%).
  • * The findings suggest that auto-HCT is a more effective treatment option in select patients with relapsed D
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Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.

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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Robust biomarkers and a complete understanding of CAR T-cell function in the postinfusion phase remain limited. Here, we used a 37-color spectral flow cytometry panel to perform high dimensional single-cell analysis of postinfusion samples in 26 patients treated with CD28 costimulatory domain containing commercial CAR T cells for NHL and focused on computationally gated CD8+ CAR T cells.

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Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients.

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Aggressive T-cell lymphomas (TCL) account for 10-15% of non-Hodgkin lymphomas (NHL) with weaker responses and shorter durations to chemotherapy than other types of NHL. Current therapies for patients with relapsed/refractory Cutaneous T-cell lymphoma (CTCL) have limited efficacy, and short durations of response. Gemcitabine and liposomal doxorubicin have shown single-agent activity in TCL and combined have activity in relapsed B-cell lymphomas.

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Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options.

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T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies.

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Cytokines are a vital component of the immune system that controls the activation and growth of blood cells. However, chronic overexpression of cytokines can trigger cellular events leading to malignant transformation. The cytokine interleukin-15 (IL-15) is of particular interest, which has been shown to contribute to the development and progression of various hematological malignancies.

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Background: Relapsed or refractory classical Hodgkin lymphoma (cHL) remains a difficult treatment challenge. Although checkpoint inhibitors (CPI) have provided clinical benefit for these patients, responses are generally not durable, and progression eventually occurs. Discovering combination therapies which maximize the immune response of CPI therapy may overcome this limitation.

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Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models.

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Background: Relapsed or refractory Hodgkin lymphoma (R/R HL) is a challenging disease with limited treatment options beyond brentuximab vedotin and checkpoint inhibitors. Herein we present the time-trend analysis of R/R HL patients who received allogeneic hematopoietic cell transplantation (allo-HCT) at our center from 2001-2017.

Methods: The patients were divided into two distinct treatment cohorts: era1 (2001-2010), and era2 (2011-2017).

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Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological disorders, but is often complicated by relapse of the underlying disease, graft-versus-host disease (GVHD), and infectious complications. We conducted a retrospective analysis on patients undergoing allo-SCT from 1984 to 2018 to better understand how survival has changed longitudinally with therapeutic advancements made to mitigate these complications. Method: We analyzed data from 1943 consecutive patients who received allo-SCT.

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