CAR T-cell therapy for secondary CNS DLBCL

Ahmed, Gulrayz; Hamadani, Mehdi; Shah, Nirav N.

doi:10.1182/bloodadvances.2021005292

Cited by 55 publications

(44 citation statements)

References 19 publications

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“… 43 – 46 One important exception might be CAR T cells with emerging data showing feasibility and efficacy, although the majority of patients still need effective bridging therapies. 38 , 47 – 49 Of the five patients in this study who received CAR T cells, two had CNS involvement and responded but one relapsed within 3 months. CAR T cells might play an important role in this setting given recent data showing superiority of certain CAR T cell products over AHCT in patients with high-risk relapsed or refractory systemic DLBCL or HGBL.…”

Section: Discussionmentioning

confidence: 93%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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Background: The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Objective: To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis. Design: A single-center retrospective analysis. Methods: We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021. Results: Fifty patients were included with a median age of 62 years; 82% had DLBCL ( n = 41) and 18% had HGBL ( n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months). Conclusion: CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.

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Section: Discussionmentioning

confidence: 93%

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Fleming

Huang

Dotson

et al. 2022

Therapeutic Advances in Hematology

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“…The available evidence suggests that CAR-T cells have good CNS activity. A single-centre retrospective study of seven patients with secondary CNS large cell lymphoma showed promising results with six patients (85%) achieving CR 21. More studies are needed to confirm the durability of remissions.…”

Section: Discussionmentioning

confidence: 99%

Durable remission with Bruton’s tyrosine kinase inhibitor therapy in a patient with leptomeningeal disease secondary to relapsed mantle cell lymphoma

Yohannan

Sridhar²,

Nguyen

et al. 2022

BMJ Case Rep

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Mantle cell lymphoma (MCL) is an incurable B cell non-Hodgkin's lymphoma with a variable clinical course. Central nervous system (CNS) involvement is a rare and dreaded complication in MCL. We report a case of leptomeningeal relapse of MCL that was successfully treated with a single-agent Bruton’s tyrosine kinase inhibitor. A man in his 50s with MCL was treated with six cycles of bendamustine–rituximab, achieving a complete remission (CR) and was subsequently placed on rituximab maintenance for 2 years. Four years later, he was hospitalised with symptoms of organic brain syndrome. Brain MRI and cerebrospinal fluid analysis confirmed CNS relapse of MCL. He was treated with dexamethasone, ibrutinib 560 mg/day and intrathecal cytarabine with improvement in neurological symptoms, and a follow-up MRI showed CR. The patient was later switched to acalabrutinib due to intolerance to ibrutinib. The patient is tolerating this regimen well, remaining in CR 3 years later.

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“…A small retrospective study also reported CR in 4 of 7 SCNSL patients receiving commercial axicabtagene ciloleucel. (88) Similarly, another series of 8 refractory SCNSL treated with tisagenlecleucel showed a CR rate of 50% with no significant toxicity. (89).…”

Section: Older/unfit Patientsmentioning

confidence: 92%

Prevention and management of secondary central nervous system lymphoma

et al. 2022

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Secondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma, or in the setting of relapse, either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%, however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of initial lymphoma diagnosis, suggesting presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL present a therapeutic challenge of control of both systemic disease and CNS disease, which uniquely requires agents that penetrate the blood brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly those presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapies containing high-dose methotrexate (HD-MTX), followed by haematopoietic stem cell transplantation have shown the most favourable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylaxis strategies and recent treatment approaches for SCNSL. The incorporation of novel agents to immunochemotherapy deserves further study in prospective trials.

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CAR T-cell therapy for secondary CNS DLBCL

Cited by 55 publications

References 19 publications

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Durable remission with Bruton’s tyrosine kinase inhibitor therapy in a patient with leptomeningeal disease secondary to relapsed mantle cell lymphoma

Prevention and management of secondary central nervous system lymphoma

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