The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma

The oncologist

article

Sahra Ali¹  Martine Muusse¹  Gro D. Håkonsen¹  Venke Skibeli¹  Maria Elisabeth Kalland¹  Ingrid Wang¹  Ingebjørg Buajordet¹  Ania Urbaniak¹  John Johnston³  Khadija Rantell³  Essam Kerwash³  Rune Kjeken²  Martina Schuessler-Lenz¹  Tomas Salmonson¹  Jonas Bergh⁶  Christian Gisselbrecht⁶  Kyriaki Tzogani¹  Irene Papadouli¹  Francesco Pignatti¹  Christiane Niederlaender³  Greg Markey³  Therese S. Saunders¹  Mona Opsata¹  Kristine Moltu¹  Bjørn Bremnes¹  Eirik Grønevik¹ 

[1] European Medicines Agency;Norwegian Medicines Agency;Medicines and Healthcare Products Regulatory Agency, United Kingdom;Paul-Ehrlich-Institut;Medical Products Agency;Scientific Advisory Group, European Medicines Agency;Department of Oncology and Pathology, Karolinska Institutet;Karolinska University Hospital BioClinicum, New Karolinska Hospital;Institut d'Hématologie, Hôpital Saint Louis

关键词: Acute lymphoblastic leukemia;    Diffuse large B-cell lymphoma;    Chimeric antigen receptor;    Kymriah (Tisagenlecleucel;    CTL019);    Replication-competent lentivirus;    Cytokine release syndrome;   

DOI  :  10.1634/theoncologist.2019-0233

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Chimeric antigen receptor (CAR)–engineered T-cell therapy is becoming one of the most promising approaches in the treatment of cancer. On June 28, 2018, the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kymriah for pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse after transplant, or in second or later relapse and for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Kymriah became one of the first European Union–approved CAR T therapies. The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy that involves reprogramming the patient's own T cells to identify and eliminate CD19-expressing cells. This is achieved by addition of a transgene encoding a CAR. The benefit of Kymriah was its ability to achieve remission with a significant duration in patients with ALL and an objective response with a significant duration in patients with DLBCL. The most common hematological toxicity was cytopenia in both patients with ALL and those with DLBCL. Nonhematological side effects in patients with ALL were cytokine release syndrome (CRS), infections, secondary hypogammaglobulinemia due to B-cell aplasia, pyrexia, and decreased appetite. The most common nonhematological side effects in patients with DLBCL were CRS, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. Kymriah also received an orphan designation on April 29, 2014, following a positive recommendation by the Committee for Orphan Medicinal Products (COMP). Maintenance of the orphan designation was recommended at the time of marketing authorization as the COMP considered the product was of significant benefit for patients with both conditions. Implications for Practice Chimeric antigen receptor (CAR)–engineered T-cell therapy is becoming the most promising approach in cancer treatment, involving reprogramming the patient's own T cells with a CAR-encoding transgene to identify and eliminate cancer-specific surface antigen–expressing cells. On June 28, 2018, Kymriah became one of the first EMA approved CAR T therapies. CAR T technology seems highly promising for diseases with single genetic/protein alterations; however, for more complex diseases there will be challenges to target clonal variability within the tumor type or clonal evolution during disease progression. Products with a lesser toxicity profile or more risk-minimization tools are also anticipated.

【 授权许可】

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