Publications by authors named "Matthew A Lunning"

Background: Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, identification and management of associated rare toxicities have become increasingly crucial.

Objective: To identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS).

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Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects.

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Unlabelled: Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.

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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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Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.

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Purpose: Significant progress has occurred in developing quantitative PET/CT biomarkers in diffuse large B-cell lymphoma (DLBCL). Total metabolic tumor volume (MTV) is the most extensively studied, enabling assessment of FDG-avid tumor burden associated with outcomes. However, prior studies evaluated the outcome of cytotoxic chemotherapy or chimeric antigen receptor T-cell therapy without data on recently approved FDA agents.

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Primary bone diffuse large B-cell lymphoma is a rare variant of extranodal non-Hodgkin lymphoma historically treated with induction chemotherapy followed by consolidative radiation therapy (RT). It remains unknown whether RT confers additional benefit following rituximab-based chemoimmunotherapy (CIT) induction in patients with limited stage disease. We conducted a multicenter, retrospective analysis of patients treated between 2005 and 2019 using rituximab-based CIT regimens with or without consolidative RT to discern whether consolidative RT adds benefit in patients with stage I-II disease that could be encompassed in one radiation field.

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ALK-positive anaplastic large cell lymphoma (ALCL) represents approximately 6-7% of the mature T-cell lymphomas. This subtype contains a translocation between the ALK gene on chromosome 2 and one of several other genes that together form an oncogene. The most frequent translocation is t(2;5) which combines ALK with NPM1.

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There remains no one standard induction for nodal-based peripheral T-cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1-10 of a 21-day cycle for six cycles of therapy followed by observation, high-dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference.

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Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting.

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Article Synopsis
  • Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare type of cancer, and this study evaluates the characteristics and outcomes in patients from North America compared to Asian reports.
  • A total of 121 patients were analyzed, with most having early-stage disease (stage I/II), showing better survival rates compared to those with advanced stages (stage III/IV).
  • Results indicate that combined modality therapy (CMT) offers similar effectiveness to radiation alone for early-stage patients, and the overall prognosis is poor regardless of race or ethnicity.*
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Background: Extranodal natural killer/T-cell lymphoma (ENKTL) is rare and clinicaldata from non-Asian countries are lacking. It is unclear whether outcomes and diseasenatural history is similar to reported Asian series. We assessed characteristics and outcomes of patients with ENKTL from major North American centers.

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Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD.

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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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Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival.

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Purpose: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches.

Methods: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS).

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Background: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas.

Methods: We did a seamless design study at 14 cancer centres in the USA.

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We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%.

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The development of chimeric antigen receptor (CAR) T-cell therapy for select hematological malignancies represents one of the most remarkable therapeutic advances in the past decade. Currently, CD19-targeted CAR T-cell therapy is approved for relapsed/refractory diffuse large B-cell lymphoma and acute lymphoblastic leukemia. However, there is significant interest in the application of CAR T-cell therapy to other hematological malignancies, including multiple myeloma, where the current focus is on the development of B-cell maturation antigen-directed CAR T-cell therapy.

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The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin μ (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL.

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