Long-Term (≥4 Year and ≥5 Year) Overall Survival (OS) By 12- and 24-Month Event-Free Survival (EFS): An Updated Analysis of ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Refractory Large B-Cell Lymphoma (LBCL)

Jacobson, Caron A.; Locke, Frederick L.; Ghobadi, Armin; Miklos, David B.; Lekakis, Lazaros J.; Oluwole, Olalekan O.; Lin, Yi; Hill, Brian T.; Timmerman, John M.; Deol, Abhinav; Reagan, Patrick M.; Stiff, Patrick J.; Flinn, Ian W.; Farooq, Umar; Goy, André; Muñoz, Javier; Siddiqi, Tanya; Shen, Rhine R.; Bot, Adrian; Dong, Jinghui; Singh, Kanwarjit; Spooner, Clare; Karalliyadda, Roshan; Kim, Jaeyeon; Zheng, Yunxiang; Neelapu, Sattva S.

doi:10.1182/blood-2021-148078

Cited by 60 publications

(48 citation statements)

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“…As previously mentioned, this concept has been moved to the clinic with the development of clinical trials with CART19 products defined with a CD4:CD8 ratio of 1 in patients with DLBCL ( 25 ). Clinical efficacy of this strategy in patients with DLBCL seems to be comparable to other CART19 studies ( 23 , 24 , 34 , 82 ), although a very low incidence of severe complications (CRS and ICANS) was noticed. Since no comparisons with other manufactured CART19 products have been done, it remains to be seen if this approach results in improved efficacy and/or toxicity in patients with DLBCL.…”

Section: Car T-cell Product Composition: the Importance Of Less Diffe...supporting

confidence: 73%

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

et al. 2022

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Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed.

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Section: Car T-cell Product Composition: the Importance Of Less Diffe...supporting

confidence: 73%

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

et al. 2022

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“…Initial approval of axi-cel in relapsed/refractory LBCL was based on ZUMA-1, a single-arm, multicenter trial of 101 patients with refractory LBCL after two or more lines of systemic therapy 23 . After 63 months of median follow-up, median OS in ZUMA-1 was 25.8 months and the 5-year OS rate was 43%, demonstrating long-term disease control with axi-cel in patients with refractory LBCL 24 . In ZUMA-1, patients who were less heavily pretreated appeared to have product CAR T cells that were potentially more biologically and clinically active 25 .…”

Section: Mainmentioning

confidence: 86%

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

Neelapu

Dickinson

Muñoz

et al. 2022

Nat Med

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182

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High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

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“…In recent years, there has been a paradigm shift in cancer treatment with the advent of effective immunotherapies that engage the patient’s immune system in the fight against the malignancy ( Waldman et al, 2020 ). CAR T-cell therapies have garnered excitement due to observed response rates in certain hematological malignancies, where they constitute potent new cancer immunotherapy options with potential for long-term patient survival ( Abramson et al, 2021 ; Adami and Maher, 2021 ; Jacobson et al, 2021 ; Schuster et al, 2021 ). CAR T-cells are genetically engineered ex vivo from the patient’s immune T-cells to express chimeric antigen receptors (CARs) that are designed to bind to selected tumor antigens.…”

Section: Introductionmentioning

confidence: 99%

CAR T-Cell Therapies in Italy: Patient Access Barriers and Recommendations for Health System Solutions

et al. 2022

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CAR T-cell therapy has emerged as a potentially transformative immunotherapy for certain B-cell malignancies including relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Unhindered and appropriate access for eligible patients is essential to enable optimal outcomes and depends on effective interplay of stakeholders and processes along the patient’s therapeutic journey. In Italy, CAR T-cell therapies have been awarded innovation status by the Italian Medicines Agency (AIFA) and were integrated into routine patient care under specific criteria. However, our analysis indicates that fewer than one in five DLBCL patients eligible under the EMA authorization, or around one in three DLBCL patients eligible under the AIFA criteria, received treatment with a licensed CAR T-cell therapy product in 2020. This publication describes key patient access barriers to CAR T-cell therapies in Italy and provides recommendations on potential solutions at the health system level.

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Long-Term (≥4 Year and ≥5 Year) Overall Survival (OS) By 12- and 24-Month Event-Free Survival (EFS): An Updated Analysis of ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Refractory Large B-Cell Lymphoma (LBCL)

Cited by 60 publications

References 0 publications

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

CAR T-Cell Therapies in Italy: Patient Access Barriers and Recommendations for Health System Solutions

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