PF299 EARLY RESPONSE OBSERVATION OF PEDIATRIC PATIENTS WITH BURKITT'S LYMPHOMA TREATED WITH CHIMERIC ANTIGEN RECEPTOR (CAR) T‐CELLS

Abstract

Background:Pediatric patients with relapsed or refractory Burkitt's lymphoma (BL) present as a major challenge due to their poor outcomes despite use of high‐intensity chemotherapy and rituximab. CAR‐T has shown efficacy in treating refractory or relapsed leukemia and non‐Hodgkin lymphoma (NHL) in adult patients.Aims:To assess the safety and efficacy of CAR‐T in the treatment of refractory or relapsed BL in pediatric patients.Methods:Our trial (ChiCTR18000144) enrolled and treated 5 patients with BL. The inclusion criteria includes: 1) The patient who didn’t get complete remission(CR)after at least 5 courses of standard chemotherapy plus CD20 mAb; and 2) The patient who didn’t get partial remission (PR) or showing progression after 2 courses of second‐line chemotherapy; and 3) High expression of at least one B cells markers (CD19/CD20/CD22) examined by immunohistochemistry. The highest expressed marker was chosen as first round CAR‐T target. The therapeutic doses of CAR‐T range from1∗10^6 to 3∗10^6 per kilogram of body weight each course. The effects and adverse events of CART cells after infusion were observed. The change of CAR‐T cells and cytokines were measured weekly. Tumor response was evaluated at day 30 and day 60 post infusion and every two months afterwards.Results:Five patients aged 6 to 10 years with a median age of 8 years, were enrolled, including 4 male (80%) and 1 female (20%). St Jude staging at the time of diagnosis: 3 cases (60%) in stage III, 2 cases (40%) in stage IV, 1 case of CNS invasion (20%), 1 case of bone marrow invasion (20%) and none in stage I or stage II.Five patients were treated with 1 to 3 rounds of CAR‐T. The overall response rate (OR) was 100%. Three cases (60%) achieved CR by one round of CD19 CAR‐T cell therapy, while two cases (40%) achieved PR with CD19 CAR‐T treatment and achieved CR after subsequent treatment with CD22 or CD22 and CD20 CAR‐T.During the treatment, fever, gastro‐intestine discomfort, rash, capillary leak syndrome, Immunopneumonia, tremor, hypotension, Immunocytopenia abnormal coagulation, liver dysfunction, and other toxic effects occurred. One patient (20%) was diagnosed of cytokine‐release syndrome(CRS) grading I and the other four grading III. All cases recoverd fully after active symptomatic and supportive treatment (including application of glucocorticoids in CRS grading III). There were no death events.The last follow‐up was January 30, 2019. The longest follow‐up duration was 382 days, the shortest 62 days, and the median was 249 days. Currently, all patients were in event‐free survival.Summary/Conclusion:CD19/CD20/CD22‐CAR‐T therapy shows robust efficacy in pediatric patients with refractory and relapsed BL and the toxic and adverse effects are moderate and can be well controlled.