Publications by authors named "Locke F"

Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge.

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Background: Relapsed and refractory Diffuse large B cell lymphoma (DLBCL) can be successfully treated with axicabtagene ciloleucel (axi-cel), a CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy. Diagnostic image-based features could help identify the patients who would clinically respond to this advanced immunotherapy.

Purpose: The aim of this study was to establish a radiomic image feature-based signature derived from positron emission tomography/computed tomography (PET/CT), including metabolic tumor burden, which can predict a durable response to CAR-T therapy in refractory/relapsed DLBCL.

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Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection.

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Ionizing radiotherapy (RT) is a widely used palliative and curative treatment strategy for malignancies. In solid tumors, RT-induced double strand breaks lead to the accumulation of indels, and their repair by non-homologous end-joining has been linked to the ID8 mutational signature in resistant cells. However, the extent of RT-induced DNA damage in hematologic malignancies and its impact on their evolution and interplay with commonly used chemotherapies has not yet been explored.

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We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.

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Background: Human herpesvirus 6B (HHV-6B) frequently reactivates following allogeneic stem cell transplant (alloHCT). Consensus guidelines note that haploidentical alloHCT may represent a high-risk population for which there is little evidence; this warrants further investigation.

Methods: In this single-center retrospective study, we evaluated 188 consecutive adult patients receiving haploidentical alloHCT between 11/2014 and 11/2020 and compared outcomes between patients with HHV-6B reactivation receiving targeted antiviral therapy and those who were clinically observed.

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Article Synopsis
  • Ciltacabtagene autoleucel (cilta-cel) CAR-T therapy was approved in 2022 for treating patients with multiple myeloma who have not responded to other treatments.
  • Out of 255 patients, 236 received the therapy, and many of them didn't qualify for earlier trials, but the results were still positive.
  • Most patients experienced some side effects, but many showed good responses to the treatment, with a significant percentage remaining cancer-free after one year.
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  • * Patients reported improvements in physical functioning and fatigue within a year post-treatment, but indicators of pain, anxiety, and depression remained stable or worsened in those with active disease.
  • * While overall toxicity decreased for the first 180 days, it increased again by day 360; prior therapies influenced worsening pain and anxiety in patients with extensive treatment histories.
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Article Synopsis
  • - Axicabtagene ciloleucel (axi-cel) is an approved CAR T-cell therapy for relapsed/refractory large B-cell lymphoma, but it often causes side effects like cytokine release syndrome (CRS) and neurological events (NEs).
  • - To investigate ways to reduce these toxicities, the ZUMA-1 trial included a safety cohort (Cohort 3) that used the drug tocilizumab and anticonvulsant levetiracetam as preventive measures during treatment.
  • - In a 24-month follow-up of 42 patients in Cohort 3, 92% experienced any-grade CRS and 87% had NEs, while the overall response rate was 63
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Article Synopsis
  • Autologous anti-CD19 CAR T cells are becoming standard treatment for relapsed/refractory large B-cell lymphoma, but serious side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS) pose risks, often requiring ICU care.
  • In a study involving 925 patients in France, high rates of CRS (84.1%) and ICANS (40.5%) were observed, with significant proportions experiencing severe forms of these conditions.
  • Two prognostic scoring systems (CRS-PSS and ICANS-PSS) were developed to identify patients at higher risk for severe CRS and ICANS based on specific clinical factors, and these scores were validated in other patient groups treated with similar therapies.
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Purpose: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy.

Methods: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.

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Multiple chimeric antigen receptor (CAR) T-cell therapies are US Food and Drug Administration-approved, and several are under development. Although effective for some cancers, toxicities remain a limitation. The most common toxicities, that is, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, are well described.

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Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions.

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Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.

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Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications.

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Nodal peripheral T cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-HCT) as a consolidation strategy following initial chemotherapy response remains uncertain. This study aims to evaluate the impact of upfront auto-HCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy.

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Introduction: Studies have compared chimeric antigen receptor (CAR) T-cell therapies and salvage chemotherapy in relapsed/refractory large B-cell lymphoma (LBCL) patients, but further evidence of their relative effectiveness is warranted.

Methods: Our systematic review identified studies comparing efficacy and safety outcomes of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel) and tisagenlecleucel (tisa-cel) trials to salvage chemotherapy cohorts in LBCL patients with ≥2 prior lines of treatment; and an extended evidence network included indirect comparisons comparing CAR T-cell therapies. We conducted network meta-analyzes using Bayesian hierarchical modeling.

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Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings.

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Article Synopsis
  • Metabolic tumor volume (MTV), measured via PET scans, is a potential indicator of prognosis in large B-cell lymphoma (LBCL) patients, particularly in assessing how tumor burden affects treatment outcomes.
  • The ZUMA-7 study compared outcomes between patients receiving axicabtagene ciloleucel (axi-cel) and standard care, revealing that those with lower MTV (median or less) generally had better event-free survival (EFS) and progression-free survival (PFS) across both treatments.
  • Patients with high MTV showed poorer survival rates and more severe side effects, emphasizing the need for assessing MTV as a predictor of treatment response in future LBCL therapies.
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  • Advancements in CLL/SLL treatments have led to a study exploring a new frontline therapy combining high-dose methylprednisolone, ofatumumab, and lenalidomide for treatment-naive patients.
  • In a phase 2 study involving 45 patients, the treatment showed a 96% overall response rate and a median progression-free survival of 54.4 months, with 29% achieving a complete response.
  • Although the treatment was generally well tolerated, with manageable side effects, the effectiveness compared to existing treatments remains uncertain, highlighting the need for further research in the frontline setting.
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Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study).

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The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation.

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