A Pilot Study of Axicabtagene Ciloleucel (axi-cel) for the Treatment of Relapsed/Refractory Primary and Secondary Central Nervous System Lymphoma (CNSL)

Jacobson, Caron A.; Falvey, Caroline; Bouvier, Riemke; Hogan, Sarah; Kendricken, Elizabeth; Jones, Julia; Grimm, Elizabeth A.; Redd, Robert A.; Lee, Eudocia Q.; Castro, Luis Gonzalez; Chukwueke, Ugonma; Figueroa, Jose McFaline; Kim, Austin I.; Torres, Alexandra; Ramsdell, Linda; Kean, Leslie S.; Gerdemann, Ulrike; Albanese, Alexandre; Keskula, Paula; Meredith, David M.; Sholl, Lynette M.; Poddar, Soumya; Davis, Madison; Mao, Daquin; Filosto, Simone; Mattie, Mike; Armand, Philippe; Nayak, Lakshmi

doi:10.1182/blood-2022-165256

Cited by 16 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CAR-T cells therapy also demonstrated an acceptable safety profile in R/R PCNSL across several studies, with no increased risk of severe ICANS; however, the overall incidence of neurological toxicity seems to be slightly higher among these patients in comparison to the historical rate [76][77][78].…”

Section: Car-t Cellsmentioning

confidence: 94%

“…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%

“…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. PD-1, CD69) and to have an IFNγ gene signature [78]. These changes in gene expression occur following entry into the CNS and are unrelated to disease burden, contributing to a better understanding of CART cells mechanism of action.…”

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

confidence: 99%

See 2 more Smart Citations

New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

View full text Add to dashboard Cite

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.

show abstract

Section: Car-t Cellsmentioning

confidence: 94%

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

confidence: 99%

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

confidence: 99%

See 1 more Smart Citation

New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

View full text Add to dashboard Cite

show abstract

“…PD1 blockers, nivolumab and pembrolizumab show clinical benefit in a small cohort of patients 62 and trial are ongoing (NCT02857426, NCT02779101). Chimeric antigen receptor (CAR) T‐cell therapy intravenously or intraventricularly show promising results in early phase studies with a good safety profile 63–66 although durability and long‐term cognitive performance remains to be defined. Trials are ongoing (NCT04443829, NCT03484702, NCT04608487, NCT04464200).…”

Section: Novel Therapies In Pcnsl/scnslmentioning

confidence: 99%

Management of primary and secondary CNS lymphoma

Khwaja

Cwynarski

2023

Hematological Oncology

View full text Add to dashboard Cite

Central nervous system (CNS) lymphoma has traditionally had very poor outcomes however advances in management have seen dramatic improvements and long‐term survival of patients. In primary CNS lymphoma there are now randomised trial data to inform practice, however secondary CNS lymphoma has a lack of randomised trial data and CNS prophylaxis remains a contentious area. We describe treatment strategies in these aggressive disorders. Dynamic assessment of patient fitness and frailty is key throughout treatment alongside delivery of CNS‐bioavailable therapy and enrolment in clinical trials. Intensive high‐dose methotrexate‐containing induction followed by autologous stem cell transplantation is preferred for patients who are fit. Less intensive chemoimmunotherapy, whole brain radiotherapy and novel therapies may be reserved for patients unfit or chemoresistant. It is essential to better define patients at increased risk of CNS relapse, as well as effective prophylactic strategies to prevent it. Future prospective studies incorporating novel agents are key.

show abstract

“…9 Another clinical trial of CD28 CAR T-cells in patients with primary or secondary CNS lymphoma is ongoing. 10 Data on the safety of CD28 CAR T-cells in other B-cell malignancies, such as B-ALL and MCL, are even more scarce. 6 Additionally, none of these studies evaluated the safety of outpatient administration of CAR T-cells in patients with CNS involvement.…”

mentioning

confidence: 99%

Outpatient CD28‐costimulated CAR T‐cells for B‐cell malignancies with CNS involvement

Sanber

Ondo

et al. 2023

American J Hematol

View full text Add to dashboard Cite

There are limited data on the safety of chimeric antigen receptor (CAR) T-cells with the CD28 co-stimulatory domain (CD28 CAR T-cells), such as axicabtagene ciloleucel (Axi-cel) or brexucabtagene autoleucel (Brexu-cel), in patients with active or prior central nervous system (CNS) involvement. Due to concerns over the risk of immune effector cell-associated cytotoxicity (ICANS), patients with CNS disease were largely excluded from the pivotal ZUMA trials that led to the approval of CD28 CAR T-cells for diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and B-cell acute lymphoblastic leukemia (B-ALL). 1 Although anecdotal and small retrospective reports have been published, 2-6 the safety of CD28 CAR T-cell therapy in patients with CNS involvement has not been adequately evaluated. Furthermore, the safety and feasibility of outpatient administration of CAR T-cells for patients with active or prior CNS involvement remain unclear. Herein, we report on our institutional experience with outpatient CD28 CAR T-cell administration in 10 consecutive patients with CNS involvement. We performed a retrospective analysis of outcomes for all patients who received commercially available CD28 CAR T-cells at Johns Hopkins Hospital between January 2019 and November 2022 for B-cell malignancies with previously treated or active CNS involvement. The study was approved by the Institutional Review Board of Johns Hopkins. Patients were considered to have active CNS disease if they had radiographic evidence of CNS involvement or malignant B-cells detectable by flow cytometry in the cerebrospinal fluid (CSF)

show abstract

A Pilot Study of Axicabtagene Ciloleucel (axi-cel) for the Treatment of Relapsed/Refractory Primary and Secondary Central Nervous System Lymphoma (CNSL)

Cited by 16 publications

References 0 publications

New hopes in relapsed refractory primary central nervous system lymphoma

New hopes in relapsed refractory primary central nervous system lymphoma

Management of primary and secondary CNS lymphoma

Outpatient CD28‐costimulated CAR T‐cells for B‐cell malignancies with CNS involvement

Contact Info

Product

Resources

About