CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network

Alcantara, Marion; Houillier, Caroline; Blonski, Marie; Rubio, Marie‐Thérèse; Willems, Lise; Rascalou, Agathe Waultier; Garff‐Tavernier, Magali Le; Maloum, Karim; Bravetti, Clotilde; Souchet, Laëtitia; Roos‐Weil, Damien; Morel, Véronique; Uzunov, Madalina; Metz, Carole; Dhib-Charfi, Meriem; Nguyen, Stéphanie; Shor, Natalia; Psimaras, Dimitri; Weiss, Nicolas; Jacque, Nathalie; Solorzano, Silvia; Gauthier, Nicolas; Cann, Marie Le; Norol, Françoise; Soussain, Carole; Choquet, Sylvain

doi:10.1182/blood.2021012932

Cited by 44 publications

(37 citation statements)

References 21 publications

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“…In our study, CD19-specific CAR-T cell-based therapy for R/ R secondary CNSL resulted in a CNS ORR of 73.3%, and a CR rate of 60%, which were similar to the response of Tisagenlecleucel, Axicabtagene cells in the previous reports (13,28,29), and the sequential CD19/CD22 CAR-T cell immumotherapy following ASCT (30).…”

Section: Discussionsupporting

confidence: 89%

Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Zhang

Zhang²,

Wang³

et al. 2022

Front. Immunol.

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Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response.

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Section: Discussionsupporting

confidence: 89%

Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Zhang

Zhang²,

Wang³

et al. 2022

Front. Immunol.

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“…65,66 Results from multiple case series have shown CAR T-cell therapy activity in primary CNS lymphoma and secondary CNS lymphoma, suggesting the potential to greatly improve outcomes for these patients. 67,68 Although further CAR T-cell studies are needed, this therapeutic strategy could influence the risk-to-benefit balance when making decisions around CNS prophylaxis, but it is recognised that performance status might preclude eligibility and, in many countries, it is not readily available due to cost and resource impact.…”

Section: Arguments Against High-dose Methotrexatebased Prophylaxismentioning

confidence: 99%

CNS prophylaxis for diffuse large B-cell lymphoma

Eyre

Savage

Cheah

et al. 2022

The Lancet Oncology

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“…Recently, some studies indicated that CD19CAR-T therapy had effective outcome in refractory CNSL patients with the controllable ICANS [130][131][132][133]. A prospective phase I/II study was conducted to treat R/R PCNSL patients with tisagenlecleucel (tisa-cel) at the FDA-approved dose of (0.6-6.0) × 10 8 CAR-T cells.…”

Section: Application Of Immune Cell Therapymentioning

confidence: 99%

“…Medium onsets of CRS and ICANS after infusion were 5 and 8 days, respectively. ICANS ≥ grade 3 occurred in 2/9 patients (1 axi-cel, 1 tisa-cel) [130]. In another retrospective cohort enrolling patients with CD19 + R/R NHL and chronic lymphocytic leukemia, a CAR construct containing a CD28 costimulatory domain and coexpressing truncated epidermal growth factor receptor was used to generate CD19CAR-T cells.…”

Section: Application Of Immune Cell Therapymentioning

confidence: 99%

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

et al. 2022

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Primary central nervous system lymphoma (PCNSL) is a type of central nervous system restricted non-Hodgkin lymphoma, whose histopathological diagnosis is majorly large B cell lymphoma. To provide specific, evidence-based recommendations for medical professionals and to promote more standardized, effective and safe treatment for patients with PCNSL, a panel of experts from the Chinese Neurosurgical Society of the Chinese Medical Association and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association jointly developed an evidence-based consensus. After comprehensively searching literature and conducting systematic reviews, two rounds of Delphi were conducted to reach consensus on the recommendations as follows: The histopathological specimens of PCNSL patients should be obtained as safely and comprehensively as possible by multimodal tomography-guided biopsy or minimally invasive surgery. Corticosteroids should be withdrawn from, or not be administered to, patients with suspected PCNSL before biopsy if the patient’s status permits. MRI (enhanced and DWI) should be performed for diagnosing and evaluating PCNSL patients where whole-body PET-CT be used at necessary time points. Mini-mental status examination can be used to assess cognitive function in the clinical management. Newly diagnosed PCNSL patients should be treated with combined high-dose methotrexate-based regimen and can be treated with a rituximab-inclusive regimen at induction therapy. Autologous stem cell transplantation can be used as a consolidation therapy. Refractory or relapsed PCNSL patients can be treated with ibrutinib with or without high-dose chemotherapy as re-induction therapy. Stereotactic radiosurgery can be used for PCNSL patients with a limited recurrent lesion who were refractory to chemotherapy and have previously received whole-brain radiotherapy. Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy.

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CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network

Cited by 44 publications

References 21 publications

Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

CNS prophylaxis for diffuse large B-cell lymphoma

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

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