P1460: Safety and Efficacy Findings of Auto1, a Fast-Off Rate Cd19 Car, in Relapsed/Refractory Primary CNS Lymphoma

Roddie, Claire; Dias, Juliana Bernardes Elias; O’Reilly, Maeve; Green, L.; Vaughan, Megan; Agliardi, Giulia; Garcia, Jose M. Prieto; Lewin, Evie; Lowdell, M.; Mitsikakou, Marina; Charalambous, Efrosini; Hotblack, Alastair; Dreau, Hélène; Marzolini, Maria A V; Wood, L. Michael; Every-Clayton, C.; Lal, Alka; Ngai, Y.; Popova, B.; Malhi, Amarveer; Kunaseelan, Sangeetha; Spanswick, Victoria J.; Lowe, Helen; Ensell, Leah; Hartley, Julie; Domning, Sabine; Thorne, L; Hyare, Harpreet; Murphy, Patrick; Linch, David C.; Fox, Colin; Peggs, Karl S.; Cwynarski, Kate; Pulé, Martin

doi:10.1097/01.hs9.0000848696.94414.98

Cited by 2 publications

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“…In fact, the ability of intravenous (IV)-delivered CART cells to expand in the peripheral blood and hence cross the BBD was demonstrated by a number of reports and retrospective studies [73–76]. Not only these findings were confirmed in prospective trials evaluating the safety and efficacy of CART cells for the treatment of PCNSL, but also some aspects were further elucidated by exploratory correlatives including flow cytometry, RNA sequencing and cytokine profiling [77–79]. Interestingly, an ongoing pilot study of Axicabtagene ciloleucel (axi-cel) for the treatment of R/R Primary and Secondary CNS Lymphoma has shown that CART cells in the CSF greatly differ from their peripheral blood counterpart and are more likely to be CD4 + , to express activation markers (e.g.…”

Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 99%

New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

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Purpose of review Patients with relapsed/refractory primary central nervous system lymphoma (rrPCNSL) have poor prognosis, with a median survival after relapse of 6.8 months. In this review, we discuss the evolving landscape and the possible future directions related to this important unmet clinical need. Recent findings The modern two-phase approach for newly diagnosed PCNSL based on an induction using high-dose methotrexate (HD-MTX) combinations and a subsequent consolidation, has significantly improved the outcome in this setting. However, this strategy is able to cure more or less 50% of patients. rrPCNSL patients have a very poor prognosis with a reported 5-year overall survival of 18%. Late relapses (after third year) and use of high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) represent important factors associated with a better outcome in this setting. On the basis of the growing acquisition of knowledge on the molecular characteristics of PCNSL, the use of non-chemotherapeutic drugs such as bruton tyrosine kinase inhibitors (BTK-is), immunomodulatory drugs (IMiDs) and immune checkpoint blockers (ICBs) is increasing in the last years along with the introduction of novel approaches (CAR-T cells and blood--brain barrier disruption). However, despite high responses in some cases, durations are often short, translating in outcome results still unsatisfactory. Summary Treatment of rrPCNSL patients is challenging. As no standard of care exist in this setting, it is of paramount importance to acquire new knowledge related to this condition and start multidisciplinary collaboration in order to improve pts outcome.

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Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 99%

New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

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“…Among twelve patients infused, six obtained a CR (50%) and, with a median follow up of 12 months, three patients were still in remission at the data cut-off. The ongoing phase I CAROUSEL trial investigates AUTO1—a novel CAR-T cell product characterized by a fast off-rate CD19-binding domain—in patients with R/R PCNSL [ 47 ]. The trial includes a conditioning regimen enriched by a dose of the anti-PD1 antibody pembrolizumab, with the aim of enhancing CAR-T cell expansion, and an additional intraventricular administration of AUTO1 thorough the Ommaya reservoir for patients not achieving a response after the intravenous infusion.…”

Section: Extending the Setting For Large B-cell Lymphomamentioning

confidence: 99%

Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

Benevolo Savelli,

Clerico,

Botto

et al. 2023

Cancers

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In the last decade, anti-CD19 CAR-T cell therapy has led to a treatment paradigm shift for B-cell non-Hodgkin lymphomas, first with the approval for relapsed/refractory (R/R) large B-cell lymphomas and subsequently for R/R mantle cell and follicular lymphoma. Many efforts are continuously being made to extend the therapeutic setting in the lymphoma field. Several reports are supporting the safety and efficacy of CAR-T cells in patients with central nervous system disease involvement. Anti-CD30 CAR-T cells for the treatment of Hodgkin lymphoma are in development and early studies looking for the optimal target for T-cell malignancies are ongoing. Anti-CD19/CD20 and CD19/CD22 dual targeting CAR-T cells are under investigation in order to increase anti-lymphoma activity and overcome tumor immune escape. Allogeneic CAR product engineering is on the way, representing a rapidly accessible ‘off-the-shelf’ and potentially more fit product. In the present manuscript, we will focus on recent advances in CAR-T cell therapy for lymphomas, including new settings and future perspectives in the field, reviewing data reported in literature in the last decade up to October 2023.

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P1460: Safety and Efficacy Findings of Auto1, a Fast-Off Rate Cd19 Car, in Relapsed/Refractory Primary CNS Lymphoma

Cited by 2 publications

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New hopes in relapsed refractory primary central nervous system lymphoma

New hopes in relapsed refractory primary central nervous system lymphoma

Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

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