Publications by authors named "Joseph McGuirk"

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR T cell therapy approved for the treatment of relapsed/refractory large B-cell lymphoma (LBCL). We present a multicenter retrospective study evaluating safety, efficacy, and resource utilization of liso-cel in the standard-of-care setting. Patients received commercial liso-cel at 7 US medical centers and patient selection, toxicity management, and disease assessment followed institutional practices.

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Article Synopsis
  • CAR T-cell therapy shows strong initial results for treating relapsed refractory multiple myeloma, but most patients eventually relapse, often within 5 months.
  • In a study of 139 patients who relapsed after CAR T-cell therapy, different salvage therapies were analyzed, revealing that bispecific antibodies, like talquetamab and teclistamab, had the best overall and complete response rates.
  • The presence of extramedullary disease at relapse was linked to poorer outcomes, but bispecific antibodies improved survival rates, suggesting they should be the standard treatment for patients relapsing after CAR T-cell therapy.
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Background: Recent approvals of chimeric antigen receptor T-cells (CAR T) and bispecific antibody therapies offer new hope for relapsed refractory multiple myeloma (RRMM) patients, with superior efficacy over standard regimens observed in clinical trials. However, relapse after BCMA-directed therapy is common and requires further investigation.

Patients And Methods: We conducted a retrospective cohort study on 57 RRMM patients treated with BCMA-directed CAR T.

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Background: Chimeric antigen receptor T cell (CAR-T) therapy is an emerging form of immunotherapy that has recently gained recognition for treating hematological malignancies. This successful utilization of CAR-T therapy has attracted interest in its application in refractory rheumatological diseases. Here, we will review the use of CAR-T therapy in rheumatological diseases.

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  • Idiopathic Pneumonia Syndrome (IPS) is a serious complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), potentially leading to high morbidity and mortality, often due to inflammatory damage.
  • This study examines the use of Ruxolitinib, a JAK inhibitor, combined with corticosteroids (CS) in treating IPS compared to standard corticosteroid treatment, through a case series of three patients and a systematic review of previous literature involving 346 cases.
  • Results indicated that the three patients treated with Ruxolitinib and CS showed significant improvement without mortality linked to IPS, and the systematic review supported these findings across a diverse patient demographic.
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  • 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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The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen.

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Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers.

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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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CD19-directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients.

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Introduction: Existing literature suggests that women are significantly underrepresented in the field of hematology-oncology. Women make up 35.6% of hematologists and data on females as site investigators for pivotal trials and authors in publications of pivotal trials in hematologic malignancies, specifically in the novel niche of Chimeric antigen receptor T cell (CAR-T), is sparse.

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BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients.

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Article Synopsis
  • Nivestym, a biosimilar to Neupogen, is being evaluated for its effectiveness in mobilizing peripheral blood stem cells (PBSC) in healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
  • A retrospective study analyzed data from 541 donors who received either Nivestym or Neupogen, focusing on factors like donor age, weight, and various counts of cells before and after treatment.
  • Results showed that while Nivestym was generally as effective as Neupogen for PBSC mobilization, younger donors (under 35) had a slightly lower CD34 cell count after using Nivestym compared to those using Neupogen.
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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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The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T.

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Chimeric antigen receptor T-cell (CAR T-cell) therapy has changed the paradigm of management of non-Hodgkin's lymphoma (NHL) and Multiple Myeloma. Infection complications have emerged as a concern that can arise in the setting of therapy and lead to morbidity and mortality. In this review, we classified infection complications into three categories, pre-infusion phase from the time pre- lymphodepletion (LD) up to day zero, early phase from day of infusion to day 30 post-infusion, and late phase after day 30 onwards.

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Background: The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy.

Methods: We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States.

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Chimeric antigen receptor T cell therapy (CAR-T) and bispecific T cell engagers (TCE) for multiple myeloma (MM) are readily available at many large US medical centers. However, many potentially eligible patients may not be referred to the specialized centers administering these therapies. Perspectives regarding potential barriers for MM cellular therapy from referring-center oncologists (ROs) versus treating-center oncologists (TOs) have not been reported previously.

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Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients.

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This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints.

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Background: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT).

Methods: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28.

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We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov.

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