Study Of Efficacy,safety And Pharmacokinetic Characteristics Of Lenalidomide Combined With Low-dose Dexamethasone In The Treatment Of Relapsed Refractory Multiple Myeloma

Background Multiple myeloma(MM)is a hematologic disorder characterized by abnormal proliferation of plasmacytes.Those plasmacytes secret monoclonal immunoglobulin or the fragments,leading to relative organ or tissue injure.Although enormous advances with the appearance of Proteasome inhibitors(PIs),immunomodulatory drugs(IMi Ds)and autologous stem cell transplantation(ASCT),MM remains incurable due to cytogenetic heterogeneity.Lenalidomide is a second-generation immunomodulatory.It works on MM by reducing proliferation and inducing apoptosis of tumor cells,and activating immunologic effector cells.Several critical phase III clinical trials(MM-009,MM-010,MM-021)have shown the significant clinical benefits by using lenalidomide combining with low-dose dexamethasone.However,those factors,which may affect prognosis of relapsed or refractory multiple myeloma(RRMM)patients treated with lenalidomide combining with low-dose dexamethasone,are not consistent in these studies.Objective To evaluate the efficiency,safety and pharmacokinetics of lenalidomide combining with low dose dexamethasone in RRMM patients,and analyze the factors that may affect prognosis of RRMM patients.Methods In this study,42 patients with RRMM in Henan Cancer Hospital from October2016 to December,2019 were collected and the follow-up date was up to Dec 31,2019.The study was approved by Beijing Chao-yang Hospital Affiliated to Capital Medical University Ethics Committee(Ethics No.:LNDA201605).These patients took lenalidomide orally 25mg/d,which was adjusted based on renal function,for 21 days with a break for 7 days.Dexamethasone(40mg)was taken orally on day 1,8,15 and 22 on each cycle.Overall response rate(ORR),progess free survival(PFS),overall surval(OS),duration of remission(DOR)and disease control rate(DCR)were calculated for efficacy analysis.Correlation of prognosis and age,renal function,revised International Staging System(R-ISS),serum lactate dehydrogenase(LDH),bone marow plasma cell ration(BMPC),bortezomide/thalidomide used or not,history of autologous stem cell transplantation,times of relapse,times of chemotherapies used before,extamedually lesions was stastistically analyzed,respectively.Safety was evaluated based on the adverse events on hematology and non-hematology.The concentration of lenalidomide in blood was measured on the 1st day of the 1st cycle to observe pharmacokinetics.Results Among 42 RRMM patients collected,38 patients could be analyzed while 4 out of them inconnected after the 1st cycle treatment.ORR was 60.5%(23/38),and47.4%(18/38)could reach PR and even above.DCR was 92.1%(35/38),median DOR was 6 months(0.6-24.0),and median PFS was 5.5 months(1.1-24.0),median PFS was 5.5 months(1.1-35.4).Univariate cox analusis was performed that the PFS was affected by extramedullary lesions,multi-times of recurrence,R-ISS,high LDH;OS was affected by extramedullary lesions,multi-times of recurrence,R-ISS stage,high LDH.Cox multivariate analysis was showed that extrameduallary invasion,R-ISS stage,high LDH,and multi-times of recurrence were independent factors of PFS for RRMM patients(P<0.05).High LDH were independent factor of OS of RRMM patients(P<0.05).The most common adverse events were anemia(52.6%),neutropenia(50.0%),and leukopenia(39.5%).The most common 3/4 level adverse events were anemia(29.0%)and neutropenia(21.0%),followed by thrombocytopenia(15.8%).For RRMM patients with normal renal function,median Tmax of lenalidomide blood concentration was 1hr,t1/2 was between 2.15-8.97 hrs,Cmax between 352-1110ng/m L,AUC0-t between 1378-10136h*ng/m L and AUC0-?between 1405-12064h*ng/m L,which were similar in Caucasian and Asian patients reported by relative studies.Conclusions1.Lenalidomide combined with low-dose dexamethasone is a highly effectively therapy with an acceptable adverse event profile for RRMM patients.2.High serum lactate dehydrogenase,R-ISS stage(III stage),extramedullary invasion are factors of poor prognostic for RRMM patients.3.For RRMM patients with first recurrence,multi-times of therapy,? 65 years,renal insufficiency,or history of bortezomib or thalidomide application,history of bortezomib or thalidomide application history of autologous stem cell transplantation,high bone marrow plasma cell ration(BMPC),lenalidomide combined with low-dose dexamethasone also shows highly efficacy.4.Pharmacokinetic characteristics of leinalidomide in this study is similar to that in previous studies on Caucasian and other Asian.