Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma

Iacoboni, Gloria; Villacampa, Guillermo; Doesum, Jaap van; Chiappella, Annalisa; Bonifazi, Francesca; López-Corral, Lucía; Aalderen, Michiel van; Kwon, Mi; Martínez-Cibrián, Núria; Bramanti, Stéfania; Reguera-Ortega, Juan Luis; Arteaga, Lina Camacho; Schmidt, Christian; Marín‐Niebla, Ana; Kersten, Marie José; García-Sancho, Alejandro Martín; Zinzani, Pier Luigi; Corradini, Paolo; Meerten, Tom van; Rejeski, Kai; Barba, Pere

doi:10.1182/bloodadvances.2021006922

Cited by 42 publications

(33 citation statements)

References 11 publications

(7 reference statements)

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“…The median time from apheresis to product delivery was 29 days, significantly longer than that reported in the ZUMA-2 trial (29 versus 16 days, p < 0.01), without any reported death prior to the receipt of CAR T product. 6 , 45 The ORR was 91% ( n = 30), and CR was observed in 79% ( n = 26) of the patients, similar to what was reported in the ZUMA-2 trial. The 1-year PFS and OS were 51% and 61%, respectively, slightly lower than the ZUMA-2 trial results.…”

Section: Introductionsupporting

confidence: 83%

CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma

Mohty

Kharfan‐Dabaja

2022

Therapeutic Advances in Hematology

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Patients with relapsed and/or refractory (R/R) follicular lymphoma (FL) and mantle cell lymphoma (MCL) have a poor prognosis with anticipated short progression-free and overall survivals. Two CD19-directed chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States for R/R FL, namely, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel. The results of ZUMA-5 and ELARA studies led to the approval of axi-cel and tisagenlecleucel, respectively, after demonstrating high overall (ORR) and complete response (CR) rates in this high-risk population of FL patients who had received a median of 3 (range = 2–4) and 4 (range = 2–13) prior lines of therapies, respectively. For instance, the ORR for ZUMA-5 was 94% (CR = 79%), and for ELARA, it was 86% (CR = 69.1%). Pertaining to MCL, brexucabtagene autoleucel is approved for R/R MCL based on results of the ZUMA-2 study. In the latter study, despite the fact that all R/R MCL patients had been exposed to prior Bruton’s tyrosine kinase inhibitors, the reported ORR was 91%, with 68% achieving a CR. These results undoubtedly demonstrate a strong efficacy of CAR T therapy in both R/R FL and MCL; yet, one must acknowledge the relatively short follow-up time of all aforementioned studies. Thus, longer follow-up showing durability of responses and long-term safety is definitely needed.

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Section: Introductionsupporting

confidence: 83%

CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma

Mohty

Kharfan‐Dabaja

2022

Therapeutic Advances in Hematology

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“…We performed a second patient stratification based on the CAR T-cell product received (Kymriah ® vs. Yescarta ® /Tecartus ® ). Kymriah ® , Yescarta ® and Tecartus ® are three second generation CAR T-products, which are characterized by the presence of one costimulatory domain, either CD28 or 4-1BB, in addition to the CD3-ς signalling domain [ 16 , 35 , 36 , 37 , 38 ]. One relevant difference is that Kymriah’s CAR contains a 4-1BB-based co-stimulatory domain, and Yescarta ® and Tecartus ® a CD28-based [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma

Wittibschlager

Bacher

Seipel

et al. 2023

IJMS

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Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019–08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09–7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68–5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells.

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“…All six patients with known TP53 mutations obtained CR post KTE‐X19, and 82% of those with blastoid morphology responded (CR 53%). To date, these initial response rates have been largely replicated in real‐world retrospective analyses 73,74 …”

Section: Aggressive MCLmentioning

confidence: 92%

How I manage mantle cell lymphoma: indolent versus aggressive disease

et al. 2023

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Summary Mantle cell lymphoma (MCL) is a mature B‐cell lymphoma with a variable clinical course and historically poor prognosis. Management is challenging in part due to the heterogeneity of the disease course, with indolent and aggressive subtypes now well recognised. Indolent MCL is often characterised by a leukaemic presentation, SOX11 negativity and low proliferation index (Ki‐67). Aggressive MCL is characterised by rapid onset widespread lymphadenopathy, extra‐nodal involvement, blastoid or pleomorphic histology and high Ki‐67. Tumour protein p53 (TP53) aberrations in aggressive MCL are recognised with clear negative impact on survival. Until recently, trials have not addressed these specific subtypes separately. With the increasing availability of targeted novel agents and cellular therapies, the treatment landscape is constantly evolving. In this review, we describe the clinical presentation, biological factors, and specific management considerations of both indolent and aggressive MCL and discuss current and potential future evidence which may help move to a more personalised approach.

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Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma

Cited by 42 publications

References 11 publications

CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma

CAR T-cell therapy for follicular lymphoma and mantle cell lymphoma

CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma

How I manage mantle cell lymphoma: indolent versus aggressive disease

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