Car-t therapy next city! Kymriah approved for lymphoma

Source: Wuxi apptec May 3, 2018 Recently, the U.S FDA approved tisagenlecleucel (kymriah) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (lbcl), including diffuse large B-cell lymphoma (DLBCL), high B-cell lymphoma and follicular lymphoma (FL), who have experienced two or more systemic therapies Kymriah is a CD19 chimeric antigen receptor T cell (car-t) immunotherapy It was jointly developed by researchers at the University of Pennsylvania and Novartis Novartis is commercialized and promoted In August 2017, kymriah became the first FDA approved cell therapy in the United States for the treatment of refractory or relapsed patients under 25 years old with B-cell precursor acute lymphoblastic leukemia (all) The recent FDA approval is based on a phase 2 clinical study called Juliet, Juliet is an open label, multicenter, single arm trial involving 27 research centers in 10 countries 160 patients with recurrent or refractory DLBCL were recruited These patients received two or more types of chemotherapy, including rituximab and anthracycline, or relapsed after HSCT Among the recruited patients, 106 received kymriah infusion The median age of 68 evaluable patients was 56 years (range 22-74 years), 71% of them were male 78% of patients had DLBCL and 22% had FL transformed DLBCL (17% was high) 44% of the patients had previously received HSCT The average number of previous treatments was 3 (range 1-6) 44% of the patients relapsed after the last treatment, 56% of the patients suffered from refractory diseases 90% of the patients received chemotherapy for lymphoid depletion, of which 66% used fludarabine and 24% used bendamostine The median time from leukocytectomy and cryopreservation to kymriah infusion was 113 days (range 47-196) A median dose of 3.5 × 108 (range 1.0-5.2 × 108) car positive survival T cells was received in the evaluable patient population ▲ the treatment process of car-t (photo source: Novartis website) shows that the overall response rate (ORR) of adult relapsed or refractory DLBCL patients treated with kymriah is 50% (95% CI, 38% - 62%), the complete response rate (CR) is 32%, and the partial response rate is 18% The median time for the reply has not been reached At least 20% of 106 patients who received infusion had all kinds of adverse events, including CRS, infection, fever, diarrhea, nausea, fatigue, hypotension, edema and headache 25% of the patients had grade 3 / 4 infection and had grade 3 / 4 thrombocytopenia (40%) and neutropenia (25%) for more than 28 days 23% of patients have severe or life-threatening CRS 18% of the patients had grade 3 / 4 neurological events These neurotoxic side effects are managed by supportive treatment 11% of patients have serious or life-threatening encephalopathy The adverse events of nervous system were not related to the death of any patients, and there was no case of brain edema leading to the death of patients "Kymriah is designed to provide doctors with a therapy that can show a lasting response in some patients with recurrent or refractory DLBCL who have undergone multiple rounds of chemotherapy, many of which have also experienced failed stem cell transplants," said Stephen J., a professor at the University of Pennsylvania School of medicine and director of the lymphoma program at Abramson cancer center "With this approval, doctors now have a meaningful treatment option to achieve and maintain long-term efficacy without stem cell transplantation, and the safety of the treatment is stable," Dr Schuster said in a statement We congratulate Novartis and hope that this treatment will bring long-term improvement to more lymphoma patients.