Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience

Ghafouri, Sanaz N.; Fenerty, Kathleen; Schiller, Gary J.; Vos, Sven de; Eradat, Herbert; Timmerman, John M.; Larson, Sarah; Mead, Monica

doi:10.1016/j.clml.2021.07.002

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…The duration of neurotoxicity was usually short, with median rates between 3 and 14 days (ranging from 1 to 70) ( 36 , 68 , 69 , 75 , 76 , 83 , 85 ). The reversibility of neurotoxic events and the full recovery of ICANS under intensive management were reported in many series ( 9 , 40 , 62 , 67 , 72 , 77 , 85 , 91 ).…”

Section: Icans In Patients With Hematologic Malignancies and Cns Invo...mentioning

confidence: 89%

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

et al. 2023

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Chimeric antigen receptor (CAR) T-cell systemic immunotherapy has revolutionized how clinicians treat several refractory and relapsed hematologic malignancies. Due to its peculiar mechanism of action, CAR T-cell-based therapy has enlarged the spectrum of neurological toxicities. CAR T-cell-associated neurotoxicity—initially defined as CAR T-cell-related encephalopathy syndrome (CRES) and currently coined within the acronym ICANS (immune effector cell-associated neurotoxicity syndrome)—is perhaps the most concerning toxicity of CAR T-cell therapy. Importantly, hematologic malignancies (especially lymphoid malignancies) may originate in or spread to the central nervous system (CNS) in the form of parenchymal and/or meningeal disease. Due to the emergence of deadly and neurological adverse events, such as fatal brain edema in some patients included in early CAR T-cell trials, safety concerns for those with CNS primary or secondary infiltration arose and contributed to the routine exclusion of individuals with pre-existing or active CNS involvement from pivotal trials. However, based primarily on the lack of evidence, it remains unknown whether CNS involvement increases the risk and/or severity of CAR T-cell-related neurotoxicity. Given the limited treatment options available for patients once they relapse with CNS involvement, it is of high interest to explore the role of novel clinical strategies including CAR T cells to treat leukemias/lymphomas and myeloma with CNS involvement. The purpose of this review was to summarize currently available neurological safety data of CAR T-cell-based immunotherapy from the clinical trials and real-world experiences in adult patients with CNS disease due to lymphoma, leukemia, or myeloma. Increasing evidence supports that CNS involvement in hematologic disease should no longer be considered per se as an absolute contraindication to CAR T-cell-based therapy. While the incidence may be high, severity does not appear to be impacted significantly by pre-existing CNS status. Close monitoring by trained neurologists is recommended.

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Section: Icans In Patients With Hematologic Malignancies and Cns Invo...mentioning

confidence: 89%

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

et al. 2023

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“…These patients received 19 salvage treatments after CAR T failure, including targeted therapy (10 treatments), immunotherapy (4), chemotherapy (3), or radiation therapy (2). A single-center analysis of 53 patients in the US with relapsed or refractory aggressive B cell lymphomas treated with CAR T between 2017 and 2020 reported that 49% (26/53) of patients were subsequently treated and that post-CAR T progression therapy commonly involved clinical trial enrollment or use of novel agents or supportive care, with no clear standard of care [ 26 ]. A two-center analysis of 34 patients treated with CAR T between 2018 and 2020 in the US found that, among the 12 patients receiving additional salvage therapy, radiotherapy (7/12), polatuzumab/bendamustine/rituximab (3/12) (Pola-BR), and pembrolizumab (3/12) were the most common [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma

Jalbert

Chen

et al. 2022

Adv Ther

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Introduction CD19-directed chimeric antigen receptor T cells (CAR T) are approved for treatment of adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) following at least two lines of therapy. Methods This study describes real-world treatment patterns after CAR T in adults with DLBCL. It includes adults diagnosed with DLBCL in IBM MarketScan Commercial and Medicare Supplemental healthcare claims databases administered CAR T between 2017 and 2019 (index event) and at least 6 months of continuous health plan enrollment pre-index. Kaplan-Meier methods were used to estimate risk and time to first subsequent treatment after CAR T, as a proxy for CAR T failure. Results Among 129 patients meeting study criteria, most (123; 95.4%) were hospitalized during CAR T therapy. Median length of stay was 17 (25th–75th percentile, 13–22) days. Estimated 6-month risk of subsequent treatment was 36.2% (95% confidence interval [CI] 27.1–45.8%). During median follow-up of 195 (25th–75th percentile, 102–362) days, median time to the first line of therapy after CAR T, accounting for censoring, was 378 days (95% CI 226, not reached). Among 48 patients who received another therapy after CAR T, 58.3% received immunotherapy, 50.0% radiation therapy, 25.0% chemotherapy, 25.0% targeted therapy, and 12.5% hematopoietic stem cell transplant. Conclusions Among real-world patients with DLBCL treated with CAR T, the risk of not achieving a durable response is considerable; additional, effective options for DLBCL salvage treatment are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02087-4.

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“…As each CAR-T-cell therapy reports actual clinical use experience as a class effect, it does not directly compare efficacy or side effects. In another report of Axi-cel (n = 45) and Tisa-cel (n = 8) therapy, the ORR and CR were 79% and 64%, respectively, with a 12-month PFS/OS of 44%/55%; as for adverse reactions, grade ≥3 CRS and ICANS accounted for 6% and 19%, respectively [52]. In a study of 36 Axi-cel-and 13 Tisa-cel-receiving patients, the CR at 100 days after CAR-T-cell infusion was 51%, followed by a six-month PFS and OS of 48% and 71%, respectively; as for adverse reactions, grade ≥3 CRS and ICANS accounted for 10% and 20%, respectively [53].…”

Section: Real-world Evidence Of Clinically Applied Car-t-cell Therapymentioning

confidence: 95%

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy

et al. 2022

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Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulated real-world evidence and the barriers associated with applying clinical trials to clinical practices from the perspective of the quality and technical aspects. After providing an overview of all the moving parts involved in the production of CAR-T-cell products, we discuss the characteristics of immune cells (given that T cells are the raw materials for CAR-T-cell therapy) and elucidate the relationship between lifestyle, including diet and exercise, and immune cells. Finally, we briefly highlight future trends in the development of immune cell therapy. These advancements may help position CAR-T-cell therapy as a standard of care.

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Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience

Cited by 16 publications

References 28 publications

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy

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