Publications by authors named "Nathan H Fowler"

Background: Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma.

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  • * New therapies, including monoclonal antibodies and CAR T-cell therapies, have been approved, but selecting the right treatment requires careful evaluation of patient-specific factors like age and remission history.
  • * An individualized approach is essential for treatment planning, and future research should focus on real-world data and understanding relapse mechanisms to improve therapy sequencing and patient selection.
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  • * The trial included 97 patients who received tisagenlecleucel, with significant estimated 24-month rates for progression-free survival (57.4%), duration of response (66.4%), and overall survival (87.7%).
  • * Biomarker analysis indicated better outcomes correlated with low levels of exhausted T cells and higher levels of naïve T cells, confirming the treatment's durable efficacy and favorable safety profile.
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  • Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are types of slow-growing non-Hodgkin lymphomas that typically have a median survival of about 20 years, but current treatments are not curative, prompting a need for new therapies.
  • A phase 2 clinical trial tested an innovative combination treatment of lenalidomide, rituximab, and ibrutinib (IRR) on previously untreated patients with FL and MZL, focusing on progression-free survival (PFS) over 24 months.
  • Results showed that after an average follow-up of about 65 months, the estimated PFS was 78.8% at 24 months and 59.7
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  • * Research using single-cell RNA sequencing revealed that patients experiencing prolonged cytopenia had an increase in specific cytotoxic T cells that produce high levels of interferon (IFN)-γ, which is linked to this condition.
  • * The findings suggest that IFN-γ negatively impacts the function of hematopoietic stem cells (which produce blood cells), and potential treatments could involve targeting IFN-γ with either thrombopoietin agonists or neutralizing antibodies.
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FOXM1 is a transcription factor that controls cell cycle regulation, cell proliferation, and differentiation. Overexpression of FOXM1 has been implicated in various cancer types. However, the activation status and functional significance of FOXM1 in diffuse large B cell lymphoma (DLBCL) have not been well investigated.

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Follicular lymphoma (FL) is generally considered an indolent disease, although patients with relapsing FL experience progressively shorter durations of response to second or later lines of therapy. The ongoing ELARA trial in adult patients with relapsed/refractory (r/r) FL treated with tisagenlecleucel demonstrated an overall response rate of 86.2% and a complete response rate of 69.

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The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory follicular lymphoma (r/r FL). As ELARA is a single-arm trial, this study compares tisa-cel outcomes from the ELARA trial with usual care from a real-world cohort. ELARA enrolled 98 patients as of 29 March 2021 (median follow-up: 15 months from enrollment).

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  • The RELEVANCE trial compared the effectiveness of lenalidomide plus rituximab (R) to rituximab plus chemotherapy (R-chemo) in patients with untreated advanced-stage follicular lymphoma (FL) over a follow-up period of 6 years.
  • Both treatment groups showed similar 6-year progression-free survival (PFS) rates of about 60% and overall survival rates of 89%, indicating that R is as effective as R-chemo.
  • The study also found no significant safety concerns, suggesting that R is a viable chemo-free option for treating previously untreated patients with FL.
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  • Follicular lymphoma (FL) is a type of B-cell cancer influenced by various immune cells, and researchers used single-cell RNA sequencing to explore its diverse cell populations and identify specific T-cell subsets.
  • They found four distinct FL subtypes, each with different T-cell characteristics linked to the expression of MHC molecules on FL cells, which impact how the immune system recognizes the tumor.
  • This study helps inform potential immunotherapy strategies by highlighting the importance of MHC expression in FL and identifying targetable immune checkpoints on T cells that vary between tumors with normal and low MHC expression.
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Patients with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART19). However, more than half of recipients will experience treatment failure. Thus, approaches are needed to identify high-risk patients who may benefit from alternative or consolidative therapy.

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Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2 in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2.

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  • PD-1 blockade using pembrolizumab combined with rituximab was tested in a phase 2 trial involving 30 patients with relapsed follicular lymphoma, showing a favorable efficacy with a 67% overall response rate and a 50% complete response rate.
  • The treatment led to some adverse events, most commonly liver enzyme abnormalities, diarrhea, and nausea, with 20% of patients needing to discontinue due to treatment-related effects.
  • Notably, a high baseline score of CD8+ T-effector cells in tumors was linked to better outcomes, highlighting the combination's potential in improving patient responses and progression-free survival.
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Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no.

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  • The study looked at a treatment, ibrutinib, for patients with a type of cancer called follicular lymphoma, finding that about 21% of patients responded well to it.
  • Researchers analyzed the genes in the patients' cancer cells to see which ones might predict who would respond to the treatment.
  • They discovered some important genes related to the patients’ responses, finding that certain genetic changes might make it harder for patients to respond to ibrutinib.
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Purpose: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination.

Patients And Methods: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide-treated patients (L-MIND).

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PI3-kinase p110δ is mainly expressed in lymphocytes and is an attractive therapeutic target in B cell lymphomas. Targeting p110β may further suppress tumor growth and overcome escape mechanisms. KA2237 is an oral, potent, dual p110β/p110δ inhibitor.

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B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations.

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Purpose: Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, exhibits improved selectivity for PI3Kδ compared with other PI3K inhibitors.

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Background: Few studies have estimated the real-world economic burden such as all-cause and follicular lymphoma (FL)-related costs and health care resource utilization (HCRU) in patients with FL.

Objectives: This study evaluated outcomes in patients who were newly initiated with FL indicated regimens by line of therapy with real-world data.

Methods: A retrospective study was conducted among patients with FL from MarketScan databases between January 1, 2010 and December 31, 2013.

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Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel).

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Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov.

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