EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma

The oncologist

article

Irene Papadouli¹  Olga Kholmanskikh²  Tim Leest²  Martina Schuessler-Lenz³  Tomas Salmonson⁴  Christian Gisselbrecht⁵  Jordi Llinares Garcia¹  Francesco Pignatti¹  Jan Mueller-Berghaus³  Claire Beuneu²  Sahra Ali¹  Benjamin Hofner³  Frank Petavy¹  Kyriaki Tzogani¹  Anne Miermont²  Koenraad Norga² 

[1] European Medicines Agency;Federal Agency for Medicines and Health Products;Paul-Ehrlich-Institut;Medical Products Agency;Hôpital Saint Louis Institut d'Hématologie;Antwerp University Hospital

关键词: Diffuse large B-cell lymphoma;    Primary mediastinal B-cell lymphoma;    Chimeric antigen receptor;    Axicabtagene ciloleucel;    Cytokine release syndrome;    CAT;    CHMP;   

DOI  :  10.1634/theoncologist.2019-0646

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

On June 28, 2018, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yescarta for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy. Yescarta, which was designated as an orphan medicinal product and included in the European Medicines Agency's Priority Medicines scheme, was granted an accelerated review timetable. The active substance of Yescarta is axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product whereby a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction using a retroviral vector to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment linked to CD28 costimulatory domain and CD3-zeta signaling domain. The transduced anti-CD19 CAR T cells are expanded ex vivo and infused back into the patient, where they can recognize and eliminate CD19-expressing cells. The benefits of Yescarta as studied in ZUMA-1 phase II (NCT02348216) were an overall response rate per central review of 66% (95% confidence interval, 56%–75%) at a median follow-up of 15.1 months in the intention to treat population and a complete response rate of 47% with a significant duration. The most common adverse events were cytokine release syndrome, neurological adverse events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. Implications for Practice Yescarta (axicabtagene ciloleucel) was the first chimeric antigen receptor T-cell therapy to be submitted for evaluation to the European Medicines Agency and admitted into the “priority medicine” scheme; it was granted accelerated assessment on the basis of anticipated clinical benefit in relapsed/refractory diffuse large B-cell lymphoma, a condition of unmet medical need. Indeed, Yescarta showed an overall response rate of 66% and a complete response rate of 47% with a significant duration and a manageable toxicity that compared very favorably with historical controls. Here the analysis of benefits and risks is presented, and specific challenges with this important novel product are highlighted, providing further insights and reflections for future medical research.

【 授权许可】

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