The Clinical Observation Of The Modified BACOD Regimen Combined With Recombinant Mutated Human Tumor Necrosis Factor For Relapsed/refractory Diffuse Large B-cell Lymphoma

Research backgroundLymphoma is a malignant tumor that originates in the lymph nodes or extranodal lymphoid hematopoietic system,which is divided into Hodgkin lymphpma(HL)and non-Hodgkin lymphoma(NHL).In China,the incidence of NHL accounts for 87.68%of all lymphomas.Diffuse large B-cell lymphoma(DLBCL)is the most common NHL subtype and the most common malignant lymphoma in adults,accounting for 30%-40%of adult NHL patients.Rituximab combined with cyclophosphamide,vincristine,doxorubicin and prednisone(R-CHOP)is the standard chemotherapy regimen for patients with DLBCL,it can achieve long-term disease-free survival in 50%-70%of patients,but 30%-50%remain incurable and develop into relapsed/refractory DLBCL(R/R DLBCL).Patients with R/R DLBCL can be treated with a second-line protocol such as the modified BACOD and R-DHAP,etc.Chimeric Antigen Receptor T cell(CAR-T)therapy can be used.Then patients can receive high-dose therapy(HDT)combined with autologous stem cell transplantation(ASCT)after achieving complete remission or better partial remission.But the patients only have 30%-50%overall response rate after a second-line protocol,and only 30%can achieve long-term survival after ASCT.Tumor Necrosis Factor-?(TNF-?)is a type ?transmembrane protein containing 233 amino acids,which is formed by the gene coding on the chromosome 6p21.3.It is a pleiotropic cytokine and can kill tumor cells directly.rmhTNF is a new type of recombinant mutated human tumor necrosis factor obtained by changing the molecular structure of TNF,with high activity and low toxic side effects.The purpose of this study is to obersve the synergistic effect and clinical adverse reactions of R/R DLBCL on rmhTNF combined with the modified BACOD regimen,and to provide more means and new ideas for the treatment of R/R DLBCL.ObjectiveTo obersve the synergistic effect and clinical adverse reactions of the modified BACOD regimen combined with rmhTNF on R/R DLBCL.MethodsFrom January 2016 to October 2019,25 R/R DLBCL patients have recieved the modified BACOD regimen combined with rmhTNF and 33 R/R DLBCL patients have received the modified BACOD regimen in the department of Hematology,Afiliated Cancer Hospital of Zhengzhou University.Patients with R/R DLBCL were statistically analyzed for case data,and observed the efficiay and adverse reactions after medication.The specific modified BACOD regimen combined with rmhTNF is:bleomycin 10mg/m2+vinblasticin 0.75mg/m2+cytarabine 150mg/m2 continuous intravenous infusion for 24 hours day 1-4,cyclophosphamide 650mg/m2 day 5 intravenous drip,and dexamethasone 10mg/m2 twice a day in day 1-5 intravenous drip and 1 million U of rmhTNF intravenous injection day 1-5.Results1.Comparison of short-term efficacy:Among the 58 patients,the ORR was 87.9%.The ORR of 25 patients who received the modified BACOD regimen combined with rmhTNF was 92%,and the ORR of 33 patients who received the modified BACOD regimen was 84.8%.There was no siginificant difference in ORR between two groups(P=0.343).Of the patients received the modified BACOD regimen combined with rmhTNF,11(44%)patients achieved CR,12(48%)patients achieved PR,2(8%)patients achieved stable disease(SD);of the patients received the modified BACOD regimen,13(39.4%)achieved CR,15(45.4%)achieved PR,and 5(15.2%)achieved SD.There was no siginificant difference in CR rate(44%vs.39.4%,P=0.466)and PR rate(48%vs.45.4%,P=0.529)between the two groups.2.Comparison of long-term survival:The median follow-up time of 58 patients was 18.5(3-43)months.The median follow-up time of the modified BACOD regimen combined with rmhTNF group and modified BACOD regimen group respectively were 20(3-43)and 18(6-41)months.The median PFS time of the modified BACOD regimen combined with rmhTNF group was not reached,and the median PFS time of the modified BACOD regimen was 14(6-38)months,the PFS rate at 2 years respectively were 61.9%and 31.3%,the difference was statistically significant(P=0.001).The median OS time of the two groups was not reached,the OS rates at 2 years of the two groups were 80.2%and 82.9%,the OS rates at 3 years of the two groups were 80.2%and 74.6%,with no significant difference(P=0.647).3.Comparison of efficacy among subgroups:Among patients recevied modified BACOD regimen combined with rmhTNF and patients recevied modified BACOD regimen,comparison of efficacy analysis found that,there was no statistically significant difference between the CR rates of the two groups in different age groups,gender,stage,IPI score,whether there was bone marrow invasion and whether there was extranodal involvement.4.Adverse reactions:The common adverse reactions of the modified BACOD regimen combined with rmhTNF were bone marrow suppression,fever,and gastrointestinal reactions.Symptoms could be relieved after corresponding symptomatic treatment.No serious adverse events happened.Conclusion1.The modified BACOD regimen combined with rmhTNF has a certain effect on relapsed/refractory diffuse large B-cell lymphoma.The adverse reactions of the modified BACOD regimen combined with rmhTNF can be tolerable.2.In relapsed/refractory diffuse large B-cell lymphoma,the modified BACOD regimen combined with rmhTNF compared with the modified BACOD regimen,can improve the patients' CR rate,PR rate,and ORR,can prolong patients' PFS,can't significantly prolong OS.