Observation On The Efficacy Of Maintenance Therapy After Autologous Hematopoietic Stem Cell Transplantation For Multiple Myeloma

BACKGROUD AND OBJECTIVE Multiple myeloma(MM)is a common malignant hematological disorder characterized by monoclonal proliferation of plasma cells.In recent years,with novel agents emerge and have resulted in enhancement of response rate and its depth in MM.High dose chemotherapy(HDCT)followed by autologos stem cell transplantation(ASCT)substantially improves PFS in MM and remains a standard of care for fit patients in the era of novel agents.Despite advances in therapeutics,achieving a cure for multiple myeloma(MM)remains challenging.Almost all patients will relapse or progress sooner or later.Maintenance treatment after autologous bone marrow transplantation in multiple myeloma improves the outcome of patients There is no best solution for maintenance treatment after ASCT for MM.The purpose of this study was to investigate the efficacy,safety and prognosis of different regimens of maintenance treatment after autologous hematopoietic stem cell transplantation for MM patients.METHODS Eighty-there MM patients in our department who underwent autologous hematopoietic stem cell transplantation and subsequent maintenance treatment have been enrolled between 2010 to June 2020.All patients were divided into thalidomide group,lenalidomide group,proteasome inhibitor group(including bortezomib and isazomib and bortezomib + thalidomide group)according to maintenance therapy.The maintenance treatment group containing lenalidomide or proteasome inhibitor is called novel agents group.Novel agents including immunomodulatory drugs and proteasome inhibitors the progression free survival(PFS)and overall survival(OS)of different maintenance treatment groups were compared.The toxic and side effects during the treatment were observed,and the clinical characteristics of the patients were analyzed by univariate and multivariate analysis.RESULTS 1.Before autologous hematopoietic stem cell transplantation,the s CR+CR rate of 83 MM patients was 26.5%,the VGPR rate was 32.5%,and the ≥VGPR rate was 59.0%.After transplantation,the s CR+CR rate was 49.4%,and the VGPR rate was 28.9%,≥VGPR rate was 78.3%.The Scr+CR rate of patients after transplantation was significantly increased(P=0.002).Compared with before transplantation,≥VGPR was significantly improved(P=0.007).2.The median follow-up time of 83 patients was 26 months(2-116 months).After autologous transplantation,the 1-and 3-year OS rates were 91.2% and 77.8%,and the 1-year and 3-year PFS rates were 77.5% and 56.3%,respectively.3.There were 23 cases of thalidomide,33 cases of lenalidomide,27 cases of proteasome inhibitors(PIs)(15 cases of bortezomib and 8 cases of isazomib,and4 cases of bortezomib + thalidomide).Objective to compare the efficacy of maintenance therapy with lenalidomide,PIs and thalidomide in MM patients after ASCT 3% in the novel agents group,47.1% in the thalidomide group,and 79.3%and 63.0% in the novel agents group and thalidomide group,respectively.Compared with thalidomide group,maintenance treatment of novel agents group after ASCT can significantly improve PFS,the difference was statistically significant(P=0.041);maintenance treatment of novel agents group after ASCT can improve OS,but the difference was not statistically significant(P=0.112),suggesting that novel agents maintenance treatment can prolong PFS of MM patients,but does not affect OS.Cytogenetic risk stratification analysis showed that novel agents maintenance therapy was more beneficial to high-risk patients and could prolong PFS,but had no effect on OS.4.During the maintenance treatment,there was no significant difference in the incidence of hematological toxicity,peripheral neuritis and other adverse reactions among the groups.5.Univariate analysis showed that serum lactate dehydrogenase(LDH)increased(P=0.034),hemoglobin decreased(P=0.004),adjusted serum calcium increased(P=0.001),high-risk group(P=0.020),and the use of new drugs(lenalidomide,proteasome inhibitor)maintenance therapy were the prognostic factors of PFS.CONCLUSION In the era of novel agents,autologous hematopoietic stem cell transplantation significantly improve the efficacy of MM.Compared with thalidomide,maintenance therapy with lenalidomide or proteasome inhibitor after autologous transplantation can further improve PFS in patients with MM and show tendency of prolongation of OS.The maintenance treatment with novel agents in the high-risk group of MM significantly improved the PFS and OS of the patients.There was no significant difference between the standard-risk group using thalidomide maintenance treatment and the novel agents maintenance treatment.High-risk cytogenetics,reduced hemoglobin,elevated blood calcium,and maintenance therapy in the novel agents group are independent prognostic factors that affect PFS after autologous transplantation in MM patients.Elevated LDH is a prognostic factor that affects OS after autologous transplantation in MM patients.