A Study Of Maintenance Therapy Using Lenalidomide For Intermediate-high Risk Diffuse Large B-cell Lymphoma

1.Purpose About two-thirds of patients with Diffuse large B cell lymphoma(DLBCL)are cured with standard R-CHOP(rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone).Although rituximab prolongs overall survival,patients with intermediate-and high-risk features still have a poor prognosis.In recent years,the use of single drug maintenance therapy can be improve survival in patients with such a kind of effective treatment strategies.Drug lenalidomide tumor cell damage and promote apoptosis of direct,antiangiogenic tumor microenvironment and multiple role in immune regulation.NCCN guidelines in the future the 2019 degrees of amine single-agent or joint rituxan,as the second line and after the treatment of choice.Therefore,this study aims to analyze first-line treatment eases in high-risk patients with DLBCL use drug lenalidomide maintenance treatment efficacy and safety,in order to to guide the future clinical application.2.Methods(1)Clinical data of medium-high risk DLBCL patients(age ≤60 years,aa IPI score 2-3or age > 60 years,IPI score 3-5)who were admitted to XXX Hospital from January2015 to October 2022 on lenalidomide monotherapy maintenance therapy were collected.All patients received 6-8 cycles of elrituximab based combination induction regimen,and the efficacy evaluation achieved Complete response(CR)or Partial response(PR)at the end of induction therapy.Patients should be given a starting dose of25 mg/day orally from day 1 to day 21 every 28 days until disease progression or recurrence or unacceptable adverse events or patient refusal,up to a maximum of 2years.(2)The primary endpoint was Progression free survival(PFS),and the secondary endpoints were Overall survival(OS),Disease free survival(DFS),2-year DFS,and adverse event assessment.(3)SPSS software(version 23.0)was used for statistical analysis;patient survival analysis was performed using Kaplan-Meier method and OS,PFS and DFS were calculated,and Log-rank test was used to analyze the difference in survival between groups.Risk factors related to recurrence or death of DLBCL patients were evaluated using Cox proportional risk model.When P < 0.05,they were considered statistically significant,and 95% Confidence interval(CI)and Haza rdratio(HR)were calculated.3.Results(1)Of the 38 patients collected in this study: 1-year PFS was 89.5%,2-year PFS was86.8%,and 3-year PFS was 68.2%.As of the last follow-up,disease relapsed in 7patients(18.4%).1-year OS is 97.4%,2-year OS is 89.2%,and 3-year OS is 85.7%.Among them,lymphoma is the leading cause of death.Other causes of death included other malignancies(1 case)and intercurrent diseases(1 case).The 2-year DFS is 71.2%.The clinical data of the control group were derived from a study of 1062 patients with DLBCL who received rituximab-based combination chemotherapy but no maintenance therapy,in which the estimated rates of 3-year PFS and OS were 58.6% and 65.1% in the intermediate-high-risk group(IPI 3 points),and the estimated rates of 3-year PFS and OS in the high-risk group(IPI 4-5 points): 55.8% and 59.0%,respectively.(2)The results of Kaplan-Meier univariate analysis showed that the immunophenotype C-myc(P=0.002)and double expression(P=0.018)were significantly correlated with PFS.The immunophenotypes Bcl-2(P=0.002),C-myc(P=0.016)and double expression(P=0.045)were significantly associated with OS.The results of Cox univariate statistical analysis showed that the immunophenotype C-myc ≥ 40%(HR=0.08;95%CI=0.10-0.61,P=0.015)and the presence of double expression(HR=0.12;95% CI= 0.02 to 0.98,P=0.048).Immunophenotype C-myc≥40%(HR=0.11;95%CI=0.01-0.94,P=0.043).Due to the small sample size and single-center retrospective case analysis study,the Cox multivariate proportional hazards regression model could not be further used to correct for confounders.(3)In this study,most of the non-hematologic adverse reactions can be controlled,mainly including fatigue,peripheral nerve damage,poor appetite,diarrhea,skin reactions,liver function and kidney function damage.The median duration of maintenance therapy with lenalidomide was 20 months(1 to 24 months).Maintenance therapy was completed in 18(47.7%)patients,and maintenance therapy was maintained in 4(10.5%)patients at the end of follow-up.Among them,neutropenia(14 cases,36.8%)and thrombocytopenia(4 cases,10.5%)were the most common hematological toxic adverse reactions.The most common grade Ⅲ./Ⅳ.adverse reactions were neutropenia(4 cases,10.5%)and skin reactions(4 patients,10.5%).2 patients(5.3%)discontinued lenalidomide due to grade Ⅲ/Ⅳ adverse reactions.There were no treatment-related deaths.4.Conclusions(1)The results of this study suggest that lenalidomide maintenance therapy prolongs PFS and OS in patients with DLBCL who are at intermediate and high risk of treatment-na(?)ve DLBCL with CR or PR.Maintenance therapy with lenalidomide may be an effective treatment for intermediate-high risk diffuse large B-cell lymphoma.(2)When lenalidomide is used maintenance therapy,patients with immunophenotype C-myc ≥ 40% or double expression may benefit.(3)In this study,there were no deaths due to lenalidomide treatment-related adverse effects,and the vast majority of adverse reactions were grade I./II.,indicating that the treatment of lenalidomide monotherapy for DLBCL was well tolerated and safe and controllable.