The Influence Of 1q21 Amplification In Patients With Newly Diagnosed Multiple Myeloma On Treatment And Prognosis

PurposeTo investigate the effect of 1q21 amplication on the responsiveness of patients accompanied with 1q21 amplication to bortezomib-based regimens,and Overall Survival(OS)and Progression Free Survival(PFS)in patients with Newly Diagnosed multiple myeloma(NDMM),and also to clarify factors independently associated with 1q21 amplication,111 NDMM patients were analyzed.MethodClinical data of newly diagnosed multiple myeloma patients admitted to Northern Jiangsu People’s Hospital from January 2015 to December 2021 were collected.All patients underwent FISH test and therapeutic effect evaluation.Patients were followed up through inpatient medical records,outpatient medical records,telephone and other contact information.Survival was assessed using overall survival(OS),which was the time from diagnosis to death of any cause or the end of follow-up.SPSS25.0 software was used.The measurement data were represented by X±S,and comparison between groups was conducted by independent sample t test or Mann Whitney U test.The classified data were represented by cases(%),and Pearson chi-square test was used for comparison between groups.Univariate and multivariate survival analysis of OS and PFS was performed by Cox regression model.log-rank test was used to compare rates between groups.Kaplan-Meier curve was used to show the incidence of cumulative survival,and logarithmic rank test was used for comparison.GraphPad-Prism9.0.0(121)software was used for plotting.Start with P≤0.05 was considered statistically significant.Results1.The basic data of 111 NDMM:Among the 111 patients,53(47.75%)were males and 58(52.25%)were females.The mean age of the patients was 65.45±8.91years.There were 6,20,42,22,1,11,9 patients with IgA κ type,IgA λ type,IgG κ type,IgD λ type,λ light chain type,κ light chain type,respectively,accounting for 5.5%,18%,37.8%,19.8%,0.9%,9.9%,8.1%,5.5%.Fluorescence in situ immunofluorescence(FISH)results showed del(17p),IGH translocation,1q21 amplification,del(13q14.3)(D13S319 gene)and del(13q14)(RBI gene)abnormal patients were 23,57,53,58 and 52,accounting for 20.7%,51.4%,47.8%,52.3%and 46.8%,respectively.1.Analysis of clinical indicators related to 1q21 amplification:The patients were divided into 1q21 amplification group and non-1q21 amplification group,including 53 patients in 1q21 amplification group and 58 patients in no-1q21 amplification group.The clinical indicators of the two groups were compared between the two groups.The results showed that the platelet count,LDH,bone marrow plasma cell proportion,D13S139 gene,RB gene,del(17p)and IGH translocation were significantly different between the two groups(P=0.001,P=0.006,P<0.001,P=0.015,P=0.002,P<0.001,P<0.001).2.Efficacy of bortezomib in 1q21 amplification group and non-1q21 amplification group:There was no significant difference in the degree of very good partial response or above(VGPR or above)after bortezomib-based therapy between 1q21 amplification group and non-1q21 amplification group(58.5%vs58.6%,P=0.786).However,the degree of partial remission(PR)or above was statistically different between the two groups(77.3%vs 89.6%,P=0.033),and the degree of PR or above was greater in the group without 1q21 amplification.3.Univariate and multivariate analysis of OS and PFS:COX univariate regression analysis showed that the single factors affecting overall survival(OS)were bone marrow plasma cell ratio,platelet count,del(17p)and 1q21 amplification(P=0.044,P=0.012,P<0.001,P<0.001).COX multivariate regression analysis showed that the independent correlation factors affecting OS were del(17p)and 1q21 amplification(P=0.028,P=0.033).COX univariate regression analysis showed that the presence of chronic diseases,del(17p)and 1q21 amplification(P=0.047,P<0.001,P=0.002)were the single factors affecting the progression-free survival(PFS).The above three factors were included in COX multivariate regression analysis,and the results showed that del(17p)and 1q21 amplification were independent indicative factors for PFS(P=0.020,P=0.044).4.OS and PFS survival analysis of the non-1q21 amplification group and the 1q21 amplification group:There were significant differences in OS and PFS between the non-lq21 amplification group and the 1q21 amplification group.The median OS were 60.5 months and 43.39 months(P<0.001),and the median PFS were 57.01 months and 39.93 months(P=0.001)respectively.5.OS and PFS survival analysis of lq21-ISS and lq21-del(17p)-ISS:1q21 amplication was included in International Staging System(ISS)to form 1q21-ISS stage groups of Ⅰ,Ⅱ and Ⅲ.The results showed that there was statistically significant difference in OS and PFS among the three groups,with median OS of 63.11 months,51.51 months and 43.63 months(P=0.018),respectively.The PFS of the three groups were 62.36 months,47.92 months and 38.79 months,respectively(P=0.019).The lq21-del(17p)-ISS predictive model was constructed by adding del(17p)to 1q21-ISS.The results showed that the median OS of the three groups was 66.00 months,53.98 months and 42.15 months,respectively(P=0.002).The median PFS of the three groups were 66.00 months,53.13 months and 37.05 months,respectively(P=0.001).Conclusions1.Newly Diagnosed MM patients with 1q21 amplification had poor prognosis,and lq21 amplification and del(17p)were independent adverse prognostic factors for OS and PFS in NDMM patients.2.NDMM patients with 1q21 amplification had a larger tumor load,and bortezomib could not overcome the adverse effects of 1q21 amplification in NDMM patients.3.lq21-ISS staging and 1q21-del(17p)-ISS staging have good prognostic value for newly diagnosed multiple myeloma patients.