Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature

Asghar, Noureen; Masood, Adeel; Dhaliwal, Armaan; Khurana, Sharad; Davis, James A.; Hashmi, Hamza; Husnain, Muhammad

doi:10.1016/j.clml.2022.09.008

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…These sites were thought to be difficult to reach limited by the blood-brain barrier or unique microenvironments, impacting cells’ ability to access and eradicate cancer cells, thus the rationale for the exclusion of persons with CNS involvement in the JULIET and ZUMA-1 trials. Recent studies including a systematic review and experiences outside clinical trials have shown CAR-T to be effective in central nervous system lymphoma ( 24 , 25 ). Similarly, case reports reporting positive experiences in myeloma have also been published ( 26 ).…”

Section: Disease Biologymentioning

confidence: 99%

Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma

Medina-Olivares,

Gómez-De León,

Ghosh

2024

Front. Oncol.

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Chimeric Antigen Receptor T-cell (CAR-T) therapies are transforming the treatment of B-cell lymphoproliferative disorders and multiple myeloma, yet global access challenges and barriers for their implementation persist. Global access disparities persist, particularly for persons living in low and middle-income countries and for underserved populations in high income countries. In this review we address patient-related factors including age, comorbidities, fitness, race and ethnicity, and geographic location for CAR-T access. Also, we review disease-related and health system barriers like disease biology, potential for short and long-term toxicity, insurance access, referrals, supply and manufacturing, regulation, costs and treatment center capacity. Lastly, alternatives for overcoming these barriers exemplified by research efforts worldwide are discussed, emphasizing the need for a multifaceted approach from all stakeholders to improve global accessibility and ensure equitable access and improved outcomes for patients worldwide.

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Section: Disease Biologymentioning

confidence: 99%

Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma

Medina-Olivares,

Gómez-De León,

Ghosh

2024

Front. Oncol.

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“…The purpose of the study was to evaluate the efficacy and safety of CAR T-cell therapy in primary and secondary relapsed/refractory CNS lymphoma. They identified that ICANS with a grade 3 or higher was present in 22% of the patients ( n = 30) ( 89 ). Finally, Cook et al performed a large, retrospective systematic review and meta-analysis including 128 patients with relapsed/refractory PCNSL ( 30 ) and SCNSL (98).…”

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

confidence: 99%

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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“…Frigault et al 8 published the first case series of 8 heavily pretreated patients with SCNSL who received tisagenlecleucel infusion, after which 4 patients achieved Central Nervous System (CNS) response where 3 patients had complete remission, and 1 had partial response (PR). Subsequent real-world studies demonstrated CAR T-cell therapy to be a promising option for patients with SCNSL involvement with a reasonable activity of CAR T-cells and an acceptable safety profile 9,10 Radiation therapy plays an important role in the management of SCNSL, for palliative or definitive intent. In terms of palliation, RT can produce prompt response and effective Local control (LC) in patients who present with severe symptoms attributable to progressive and/ or bulky disease, such as focal pain and neurological compromise.…”

Section: Radiation Therapy As Bridging and Salvage Strategy Among Pat...mentioning

confidence: 99%

Radiation therapy as bridging and salvage strategy among patients with secondary central nervous system lymphoma undergoing CD19‐targeted chimeric antigen receptor T‐cell therapy

Ababneh,

Frigault,

et al. 2023

Hematological Oncology

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Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature

Cited by 6 publications

References 23 publications

Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma

Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma

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

Radiation therapy as bridging and salvage strategy among patients with secondary central nervous system lymphoma undergoing CD19‐targeted chimeric antigen receptor T‐cell therapy

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