Successful BCMA CAR-T Therapy for Multiple Myeloma With Central Nervous System Involvement Manifesting as Cauda Equina Syndrome—A Wandering Road to Remission

Wang, Yiyun; Wang, Linqin; Zeng, Yifan; Hong, Ruoxi; Zu, Cheng; Yin, Elaine Tan Su; Zhao, Houli; Wei, Guoqing; Yang, Li; Jin, Aiyun; Hu, Yongxian; Huang, He

doi:10.3389/fonc.2021.755584

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…In accordance with our findings, two recent retrospective clinical studies by Wang et al. demonstrated the favorable clinical outcomes of BCMA CAR-T cells in several CNS-MM patients ( 9 , 14 ). The structures of CAR molecules in these reports and our study were similar, as the second-generation CAR with murine scFv and 4-1BB co-stimulatory domain was utilized.…”

Section: Discussionsupporting

confidence: 93%

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion

Wang

He²,

Yang

et al. 2022

Front. Oncol.

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BackgroundMultiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion.Case PresentationIn this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed.ConclusionThis case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease.Clinical Trial Registrationhttps://ClinicalTrials.gov, identifier: NCT04537442.a

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Section: Discussionsupporting

confidence: 93%

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion

Wang

He²,

Yang

et al. 2022

Front. Oncol.

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“…BCMA chimeric antigen receptor T cells (CAR-T) have also shown promising results for CNS-MM, although only a limited number of patients have been treated ( 14 , 23 – 25 ). This may prove to be a good option for the treatment of patients with CNS-MM in future.…”

Section: Discussionmentioning

confidence: 99%

Case reports: Central nervous system involvement in patients with newly diagnosed multiple myeloma

Liu

Shen²,

Liu³

2023

Front. Neurol.

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Multiple myeloma with central nervous system involvement (CNS-MM) is rare, having a poor outcome and occurring in newly diagnosed or relapsed/refractory patients. The current report concerns 3 cases of newly diagnosed MM patients who presented with skull-derived plasmacytomas. Case 1 was a 54-year-old female patient with immunoglobulin D (IgD) subtype who developed extramedullary lesions from the sphenoid and occipital bones and the sphenoid sinus. Cases 2 and 3 had IgA subtype with left or bilateral frontal area lesions. Case 1 was treated with bortezomib, cyclophosphamide and dexamethasone (VCD) as the initial chemotherapy regimen and with bortezomib, lenalidomide, pegylated liposomal doxorubicin and dexamethasone (DVD-R) as the second line regimen. Whole-brain irradiation and intrathecal injection were given but the patient died within 9 months due to disease progression. Case 2 was treated with bortezomib, lenalidomide and dexamethasone (VRD) and received autologous hematopoietic stem cell transplantation (auto-HSCT) with a conditioning regimen of cyclophosphamide, etoposide and melphalan (CEM). Case 3 received DVD-R initially and auto-HSCT with a conditioning regimen of busulfan, cyclophosphamide, and etoposide (BuCyE). Cases 2 and 3 survived until the last follow-up more than 3 years later. Auto-HSCT with modified conditioning regimen as consolidation therapy improved the prognosis of CNS-MM.

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“…Increasing individual or short-series data related to CAR T-cell safety and ICANS in patients with CNS disease have been reported in patients with PCNSL (52), SCNSL (19,35,(53)(54)(55)(56), intravascular lymphoma (57,58), MCL (59), leukemia (39, 60-62), and myeloma (63)(64)(65)(66). Table 2 summarizes larger studies.…”

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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Successful BCMA CAR-T Therapy for Multiple Myeloma With Central Nervous System Involvement Manifesting as Cauda Equina Syndrome—A Wandering Road to Remission

Cited by 6 publications

References 25 publications

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion

Case reports: Central nervous system involvement in patients with newly diagnosed multiple myeloma

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

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