Anti CD19 car-t cell therapy! Bristol Myers Squibb LISO cel has been given priority by the US FDA in the treatment of relapsed / refractory large B-cell lymphoma

February 15, 2020 / BIOON / -- Bristol Myers Squibb (BMS) recently announced that the US Food and Drug Administration (FDA) has accepted lisocabtargene Maraleucel (Lisa cel, jcar017) has been granted a priority review on the application for permission of biological products (BLA), which is an autogenous, anti-CD19, chimeric antigen receptor (car) T-cell therapy consisting of purified CD8 + and CD4 + T cells in a specific proportion (1:1) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R / R lbcl) who have previously received at least two therapies FDA has designated the target date of PDUFA as August 17, 2020 Previously, LISO cel has been awarded breakthrough drug qualification (BTD) and regenerative medicine by FDA for the treatment of relapsed / refractory aggressive large B-cell non Hodgkin's lymphoma (NHL) Advanced treatment qualification (rmat), including DLBCL, primary mediastinal B-cell lymphoma (pmbcl), grade 3B follicular lymphoma (FL); in the European Union, LISO cel was awarded the priority drug qualification (prime) by the European Drug Administration (EMA) for the treatment of relapsed / refractory DLBCL LISO cel's BLA is based on the results of the transcend NHL 001 trial, which is the largest study to support a CD19 directed car-t cell therapy bla In this study, 269 patients with recurrent / refractory lbcl (including DLBCL) were enrolled, and the safety and efficacy of LISO cel were evaluated The results were presented at the annual meeting of the American Society of Hematology (ash) in 2019 The data showed that the overall response rate (ORR) of LISO cel was 73% (187 / 256, 95% CI: 67-78), and the complete response rate (CR) was 53% (136 / 256, 95% CI: 47-59) Remission was similar in all patient subgroups Median follow-up was 12 months (95% CI: 11.2-16.7) Median duration of remission (DOR) was not reached (95% CI: 8.6-nr) Median progression free survival (PFS) was 6.8 months (95% CI: 3.3-14.1), and median overall survival (OS) was 21.1 months (95% CI: 13.3-nr) At 12 months, 65.1% patients had no progress and 85.5% patients survived In the study, 79% (213 / 269) of all patients experienced adverse events (teaes) during ≥ Level 3 treatment, including neutropenia (60%, 161 / 269), anemia (38%, 101 / 269) and thrombocytopenia (27%, 72 / 269) Any level of CRS occurred in 42% (113 / 269) of patients, with a median of 5 days, and level 3 or higher in 2% (6 / 269) 30% (80 / 269) of the patients had nervous system events (NES), 10% (27 / 269) of the patients had grade 3 or above ne 19% and 21% of the patients received tocilizumab and corticosteroid treatment respectively LISO cel was developed by Juno, and Juno was newly acquired on the basis of US $9 billion in January 2018 It is a car-t cell therapy targeting at CD19 antigen and taking 4-1BB as co stimulatory region, in which CD4 + and CD8 + car-t cells have an accurate 1:1 ratio LISO cel represents the current best in class CD19 targeted car-t therapy, which has previously been awarded a breakthrough drug qualification by the US FDA In early January 2019, Bristol Myers Squibb announced its $74 billion acquisition of new base After a series of twists and turns, the huge acquisition was successfully completed on November 21, 2019 LISO cel is expected to become the third car-t cell therapy on the market, which is in line with Novartis, the two car-t cell therapies on the market Kymriah and Gilead yescarta target the same target, but the patients who received LISO cel treatment separated CD4 cells and CD8 cells in advance before carrying out chimeric antigen receptor (car) transduction, and then the cells after the respective transduction were retransmitted to the patients in a specific ratio of 1:1, which is better than the safety data of other car-t therapies, such as the overview of cytokine storm The rate is lower Recently, Gilead's kte-x19, another car-t therapy, has also won the priority review of the US FDA, which is an autogenous, anti-CD19, car-t cell therapy applied for the treatment of adult patients with recurrent or refractory mantle cell lymphoma (R / R MCL) MCL is a rare non-Hodgkin's lymphoma (NHL), which originates from the "mantle" cells of lymph nodes and usually affects men over 60 years old If approved, kte-x19 will become the first car-t cell therapy for MCL Kte-x19 adopts XLP manufacturing process, including T cell screening and lymphocyte enrichment For some B-cell malignancies with evidence of circulating lymphoblasts, lymphocyte enrichment is a necessary step The original source: U.S Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb's biology license app app lication (BLA) for lysobargene maraleucel (LISO CEL) for adult patients with relapsed or refractory large B-cell lymphama