CAR T- Cell Therapy Provides an Opportunity for Further Consolidation Treatment for Relapsed or Refractory Adult Burkitt Lymphoma Patients

Abstract

Background: Adult Relapsed and refractory Burkitt's progresses rapidly, and there is limited data on CART therapy. The available data also indicates poor survival rates. Aims: Exploring the efficacy of CAR-T therapy for adult relapsed/refractory Burkitt's lymphoma, and analyzing the factors affecting the efficacy and survival of CART treatment. Methods: This single-centre, retrospective study analysed patients with Burkitt's lymphoma who received CAR-T therapy at the Beijing GoBroad Boren Hospital between December 2018 and February 2023. The inclusion criteria were adult relapsed and refractory Burkitt's lymphoma. Nineteen patients were included: 13/19 (68%) male; Median age is 37 (19-56).6/18 (33%) patients get standard intense chemotherapy（not R-CHOP）.17/19 (89.4%) patients were at stage IV at the time of salvage therapy. 9/19 (47.4%) patients IPI score was ≧3 .9/19 (47.4%) patients had > 7.5 cm bulky disease. Midian Leukapheresis LDH is 547.9 U/L. Patients had received a median of 4 cycles (range 3-14) prior to treatment. 2/19 (10.5%) and 2/19 (10.5%) patients had failed prior autologous hematopoietic stem cell transplantation and prior allogeneic hematopoietic cell transplant, respectively. 17/19 (89.4%) patients received bridging therapy before CAR-T，which only have 1 patient CR and 1 patient achieve a PR. Analyzing whether a sequential consolidation treatment strategy for patients who respond to CART therapy can prolong survival. Results: The median CAR-T infusion dose is 1.46*10^6/kg（0.0126-7.22）. The median of CAR-T peak expansion is 89.5（3.84-710）*10^6/L , which occurred on day 7（7-11）after CAR-T cell therapy. 16/19（84.2%） of patients experienced CRS, with 3/19 (15.8%) of them classified as grade III-IV.Besides,5/19(15.8%) of patients experienced iCANS, with 3/19 (26.3%) of them classified as grade III-IV. The median follow-up time was 4.274 (0.2-43.4) months.Three months ORR and CRR were 31.6% and 21.1%. The best ORR and the best CRR were 47.4% and 26%, respectively. One-year progression free survival and overall survival were 15.8% and 21.1%. For individuals who achieved CR/PR to CART therapy in three months, their survival curves were significantly better than those of individuals with SD/PD. The univariate analysis of PFS showed that risk factors included the high LDH at the time of leukapheresis(p=0.0182,HR 1.001) ,three months response is SD/PD (p=0.0045,HR 20.8) and initial treatment with R-CHOP based chemotherapy(p=0.0319,HR 5.46) .Among the 19 patients, 12 patients continued to receive other treatments for consolidation or salvage, including 5 cases of other target CAR-T therapies, 5 cases of autologous transplants, and 2 cases of allogeneic transplants. However, only 4 of these all patients remained disease-free. Among them, 2 patients received allogeneic transplants, 1 patient received autologous transplant, and no subsequent other treatments in one patient. Summary/Conclusion: CAR-T therapy should be recommended as soon as possible after Burkitt becomes relapsed or refractory due to the ineffectiveness of multi-drug chemotherapy. Upon reaching remission, the transition to autologous or allogenic stem cell transplantation may be considered. Due to the small number of cases, further validation of our findings is still needed.