Impact Of Type 2 Diabetes Mellitus On The Prognosis Of Patients With Multiple Myeloma

Background:Multiple myeloma(MM)is a malignant tumor characterized by the clonal proliferation of abnormal plasma cells in the bone marrow,which leads to organ and tissue damage caused by the secretion of monoclonal immunoglobulin by malignant plasma cells.Although the clinical application of novel treatment modalities such as immunomodulators,proteasome inhibitors,and targeted monoclonal antibodies has greatly extended the survival of MM patients and improved their prognosis,multiple myeloma is highly heterogeneous,relapse and the acquisition of drug resistance are still inevitable,and early identification of risk factors that affect disease progression and prognosis is of positive significance for treatment.Recently,many studies have shown that diabetes mellitus(DM)plays an important role in the occurrence and development of various solid tumors through mechanisms such as hyperglycemia and hyperinsulinemia.Previous research on the correlation between diabetes and hematologic tumors has also indicated a certain association between diabetes and the incidence of MM.Steroids are commonly used in the chemotherapy regimens for MM,and diabetes is one of the common complications.Some scholars have proposed that diabetes caused by long-term steroid therapy and the use of some chemotherapy drugs may have adverse effects on the prognosis of hematologic tumors.At present,there are limited studies on the correlation between the previous type 2 diabetes mellitus(Type2 diabetes mellitus T2DM)and the occurrence of diabetes during treatment on the prognosis of patients with multiple myeloma.This study aims to explore the impact of type 2 diabetes mellitus on the prognosis of multiple myeloma patients by retrospectively analyzing their clinical data.Objective:This study retrospectively analyzes the clinical characteristics and prognostic factors of multiple myeloma patients who received treatment at our hospital in the past 10 years.The aim is to investigate the impact of previous co-existing type 2diabetes mellitus and the occurrence of diabetes during treatment on the overall survival and progression-free survival of multiple myeloma patients.Method:Patients with multiple myeloma who were diagnosed for the first time in the Second Affiliated Hospital of Nanchang University between January 2012 and January 2022 and underwent at least 2 cycles of chemotherapy were collected.A total of 279 patients were included in the study after screening by inclusion and exclusion criteria..After screening according to inclusion and exclusion criteria,a total of 279 patients were included in the study.The basic information,clinical data,and followup data of the patients were collected and divided into three groups: the group without T2 DM,the group with previous T2 DM,and the group with T2 DM during treatment.Clinical characteristics among the three groups were analyzed and compared.The Kaplan-Meier method was used to draw survival curves and conduct survival analysis on the three groups of patients.COX regression was used to conduct univariate analysis on various variables to identify the risk factors that affect overall survival(OS)and progression-free survival(PFS).Then,through multivariate analysis,independent risk factors that affect prognosis were identified.Results:(1)There were no significant differences(P>0.05)among the three groups in terms of gender,immune typing,light chain type,DS stage,DS subtype,stage ISS,R-ISS stage,m SMART risk stratification,whether or not to receive transplantation treatment,and whether or not to have other comorbidities and PS score.However,there were significant differences in age,BMI,and treatment plan among the three groups at the time of diagnosis.Further pairwise multiple comparisons revealed that the proportion of patients aged 60 and above in the past T2 DM group at the time of diagnosis was higher than that in the group without T2DM(P=0.01),and the proportion of overweight(BMI≥24)patients in the treated T2 DM group was higher than that in the group without T2DM(P=0.009).Moreover,the proportion of patients who received traditional chemotherapy without bortezomib in the treated T2 DM group was higher than that in the group without T2 DM or in the past T2 DM group(P=0.038,P=0.005).(2)Compared with the group without T2 DM,the group with previous T2 DM had lower PFS(P<0.001)and OS(P<0.001),and the group with T2 DM during treatment had significantly lower PFS(P=0.010)and OS(P=0.034)than the without T2 DM group;(3)The univariate analysis of OS in MM patients showed that DS stage,ISS stage,light chain type,PS score,previous T2 DM,and T2 DM during treatment were risk factors affecting OS in MM patients,and autologous hematopoietic stem cell transplantation(ASCT)treatment was a protective factor for OS in MM patients(all P<0.05).Multivariate analysis showed that PS score(HR=3.948,95%CI: 1.956-7.969,P < 0.001),ISS stage(P=0.045),and previous T2DM(HR=2.832,95%CI: 1.956-7.969,P=0.001)were independent risk factors affecting OS in MM patients,and ASCT treatment was an important protective factor for OS(HR=0.111,95%CI:0.015-0.813,P=0.030);(4)The univariate analysis of PFS in MM patients showed that DS stage,ISS stage,PS score,past T2 DM,and T2 DM during treatment were risk factors affecting PFS in MM patients.The multivariate analysis showed that PS score(HR=2.439,95%CI: 1.288-4.618,P=0.006),past T2DM(HR=3.010,95%CI: 1.918-4.725,P<0.001),and treated T2DM(HR=1.715,95%CI: 1.073-2.743,P=0.024)were independent risk factors affecting PFS in MM patients;(5)The group with T2DM(including during treatment and previous T2DM)had significantly lower PFS in both the transplantation and non-transplantation groups than the group without T2 DM.In the non-ASCT group,the median PFS of patients with T2 DM was shorter than that of the ASCT group(median PFS: 52.37 months vs.25.77 months;P<0.001),and the median PFS of the ASCT group was 96.97 months and 35.67 months,respectively(P=0.032).After adjustment,the hazard ratio(HR)in the ASCT group was 4.913(95% confidence interval(CI): 1.280-18.860,P=0.02),and the HR in the non-ASCT group was 2.194(95% CI: 1.482-3.248,P<0.001),but the difference was not statistically significant.(6)There was no significant difference in OS and PFS between patients treated with insulin and metformin(P>0.05).Conclusion:Prior history of T2 DM is an independent risk factor for OS and PFS in MM patients,and the occurrence of T2 DM during treatment is associated with poor prognosis in MM patients.