Anti CD19 car-t cell therapy! Bristol Myers Squibb LISO cel in the treatment of high-risk relapse / refractory CLL / SLL to achieve rapid MRD negative remission!

December 10, 2019 / BIOON / -- the 61st annual meeting of the American Society of Hematology (ash2019) was recently held in Orlando, Florida, USA At this meeting, BMS released the data of phase I / II transcend cl004 study on the treatment of relapsed or refractory chronic lymphoblastic leukemia or small Lymphoid Lymphoma (R / R CLL / SLL) patients with anti-CD19 car-t cell therapy lisocabatagene maraleucel (jcar017) At the end of the data period, 23 CLL / SLL patients who had received at least 3 treatments (standard risk diseases) or 2 treatments (high-risk diseases) before could be assessed for safety, and 22 patients could be assessed for efficacy The median of previous treatment was 5 (range 2-11) All patients (23 / 23) had received ibrutinib, a Btk inhibitor, and most patients (21 / 23) had relapse after treatment Nine patients (39%) failed after receiving a Btk inhibitor (progressing at the time of treatment) and venetoclax (no response at least 3 months after treatment) Most patients (83%) had high-risk features, including 17p deletion (del17p, 35%, 8 / 23) and TP53 mutation (61%, 14 / 23) After lymphocyte depletion, patients received Car + T cells to the 6th power of 50 × 10 (n = 9) or to the 6th power of 100 × 10 (n = 14) During the median follow-up of 11 months, the overall response rate (ORR) and complete response rate (CR) were 81.5% (18 / 22, 95% CI: 59.7-94.8) and 45.5% (10 / 22) respectively In patients who failed to receive a Btk inhibitor and venetoclax treatment, Orr was 89% (8 / 9, 95% CI: 51.8-99.7) and Cr was 67% (6 / 9) On the 30th day after treatment, 68% (15 / 22) of the patients had achieved early objective remission; of the 12 patients who maintained the response at 6 months, 10 had no progress at least 9 months later, and 8 had no progress at 12 months or longer In 20 patients with MRD, most of them obtained undetectable MRD in blood (75%) and bone marrow (65%) by next generation sequencing, that is, MRD negative All MRD negative patients remained in this state during the final follow-up The above results confirm that patients with relapsed or refractory CLL / SLL, including those who failed to receive ibrutinib and venetoclax treatment, who received LISO cel treatment, achieved permanent complete remission, including undetectable MRD (MRD negative) In this study, adverse events (teaes) at any level of treatment occurred in 100% (23 / 23) of patients, and 96% (22 / 23) of patients had ≥ Level 3 teaes The most common (in at least 25% of patients) teaes ≥ 3 were anemia (78%, 18 / 23), thrombocytopenia (70%, 16 / 23), neutropenia (56.5%, 13 / 23), leucopenia (43.5%, 10 / 23), febrile neutropenia (26%, 6 / 23), lymphopenia (26%, 6 / 23), and cytokine release syndrome (9%, 2 / 23) 74% (17 / 23) and 9% (2 / 23) patients experienced CRS at any level 39% (9 / 23) patients experienced any level of neuroevent (NE), 22% (5 / 23) patients experienced ≥ Level 3 Ne The median time of CRS was 4 days (range 1-10 days), and the median time of NE was 4 days (range 2-21 days) The incidence and severity of CRS and NE were similar in patients who did not respond to Btk inhibitors and venetoclax 74% (17 / 23) of the patients were treated with the anti-inflammatory drug, roacetemra / actemra (generic name: tocilizumab), and / or corticosteroids There were no level 5 incidents 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, Bristol Myers Squibb announced a $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 Original source: Bristol Myers Squibb announcements studies evaluating list cel in multiple additional patient populations, site of care and disease areas presented at American Society of Geography (ash) annual meeting