Analysis Of Clinical Characteristics,efficacy And Prognostic Factors Of IgD Multiple Myeloma

Objective: Multiple myeloma(MM)is a malignant cell clonal proliferative disease that occurs in the elderly,accounting for about 1% of all tumors and 10% of the hematological malignancies,still can not be cured.The main feature of MM is the proliferation of bone marrow plasma cells,blood and/or urine monoclonal immunoglobulin(M protein),and the typical clinical manifestations can be summarized as CRAB symptoms,hyper Calcemia,Renal dysfunction,Anemia,Bone lesions,infection caused by decreased immunity,hyperviscosity and other target organ damage.Multiple myeloma has obvious heterogeneity in biology and clinic,and the prognosis is very different.In recent years,the widespread use of immunomodulatory drugs(IMiD)and proteasome inhibitors have made great progress in the treatment of multiple myeloma,greatly improved the complete remission rate(from about 5% to more than30%)and prolong the overall survival of patients(from less than 3 years to 5-7 years).IgD type MM is a rare type of myeloma,the incidence of foreign reports about 2% and domestic reports about 8% to 10%,has a poor prognosis.At present,there is no large sample study on the clinical characteristics and survival of IgD MM in China.Therefore,this study retrospectively analyzed the clinical characteristics,curative efficacy,survival status and prognostic factors of 130 cases of IgD multiple myeloma,aimed at strengthen our study on the biological characteristics of such multiple myeloma,help clinical doctors make the right decisions during the process of diagnosis and treatment,make the stratified treatment and individualized treatment,further improve the prognosis of these patients.Methods: 130 cases of IgD MM patients admitted into our department from January 2002 to Aguest 2016 were enrolled.Among them,from January 2008 to December 2015,IgD MM patients had a total of 86 cases,while other types of MM patients over the same period a total of 838 cases.Of these 838 patients,include 411 cases of IgG MM,207 cases of IgA MM,199 cases of light chain MM,17 cases of non-secretive MM,2 cases of IgM MM and 2 cases of double clone type MM.The clinical characteristics,such as median ageat onset,light chain type,DS stage,ISS stage,Hb,PLT,creatinine,LDH,β2MG,serumcalcium,serum free light chain(sFLC)and FISH abnormalities,curative efficacy,survival status and prognostic factors of 130 cases of IgD MM patients were analyzed.To compare the clinical data of IgD and IgG and IgA MM patients in the same period(2008.01-2015.12),observed the clinical characteristics and the survival of IgD MM patients with other types of MM differences.In addition,we analyzed the consistency between IgD quantification and M protein and iFLC,the correlation between each cytogenetic abnormalities in IgD MM patients.SPSS 21.0 software was used for statistical analysis.The Kolmogorov-Smirov method was used for the normality test.Two independent samples was used the t-test and expressed as the mean ± standard deviation for the normal distribution.The non-parametric test(Mann Whitney U test)was was used for abnormal distribution,and expressed as the median.The comparison of the counting data was performed by the chi-square test or the exact probability method.The Kappa test was used for the two-class variablesconsistency.The correlation analysis was performed using Spearman correlation analysis.The Kaplan-Meier method was used for the survival analysis,and calculated survival rate by Life tablemethod.Log-rank test was used to single factor analysis,the influencing factors in single factor were included in the COX proportional regression model.P value <0.05 was considered as statistically significant.Results:(1)The median age of 130 cases of IgD MM was 55.5 years(range 33 years to 83 years),λ light chain accounts for 94.6%(123/130).Compared with the same period(2008.01-2015.12)of Ig G MM and IgA MM patients,Ⅲ phase was more common in Ig D MM when newly diagnosed,anemia(Hb: 82.5 g/L,38.0-146.0 g/L),renal dysfunction(Cr: 122.5 μmol/L,27.0-1058.0 μmol/L),high Calcium(serum Calcium: 2.48 mmol/L,1.5-4.21 mmol/L),extramedullary plasmacytoma(7.0%,6/86)were more outstanding.In addition,LDH(197.5 U/L,91.0-1622.0 U/L)levels,β2MG(6.755 mg/L,1.4-52.42 mg/L)levels,plasma cell ratio(43.0%~100%)of IgD MM was significantly higher than IgG and IgA MM patients at the same period.(2)FISH was performed in 103 IgD patients,the rate of IgH translocation,1q21 amplification,17 p deletion,13 q deletion were 82.5%(85/103),68.0%(70/103),15.5%(16/103),28.2%(29/103),respectively.For the patients with IgH translocation,we further proceeded with two-color double fusion probe hybridization about t(11;14)(q13;q32),t(4;14)(p16;q32),t(14;16)(q32;q23)and the rate of them were 45.5%(40/88),4.5%(4/88),0%(0/88).Meanwhile,we found that the positive of 1q21 amplification and t(11;14)in the IgD MM were significantly higher than the incidence of IgG and IgA MM at the same period.Then we further analyzed the correlation between 1q21 amplification,t(11;14)and other cytogenetic abnormalities.The results showed that the ratio of 1q21 amplification had a correlation with the IgH translocation ratio(r=0.3921,p<0.0001)and had no correlation with 17 p deletion and 13 q deletion(p>0.05),t(11;14)had no correlation with 17 p deletion,13 q deletion,1q21 amplification(p>0.05).(3)At the time of initial diagnosis,53 cases of IgD patients underwent serum free light chain(sFLC)detection in 138 cases,and the levels of iFLC(involved free light chain)was 1910.0mg/L(4.49~53477.0 mg/L).Compared with the iFLC levels of IgD MM and IgG MM and IgA MM patients at the same period,we found the levels of iFLC in IgD MM patients(1910.0 mg/L,4.49~53477.0 mg/L)were significantly higher than those in IgA(269.9 mg/L,2.10~30027.0 mg/L)and IgG MM(524.0 mg/L,1.01~24569.0 mg/L)patients,p<0.0001.(4)There are 28 cases patients with both the IgD quantitative and serum free light chain detection in 130 cases of IgD MM.In this 28 cases of IgD MM,IgD levels,M protein,iFLC levels decreased ≥ 90% / 50%~89% / < 50% were 6/14/8 cases,9/12/7 cases,8/13/7 cases after 2 chemotherapy cycle,respectively.And IgD levels,M protein,iFLC levels decreased ≥ 90% / 50%~89% / < 50% were 14/8/6 cases,15/7/6 cases,10/14/5 cases after 4 chemotherapy cycle,respectively.The Kappa test showed after 2 chemotherapy cycle,KappaIgD/Mprotein=0.447,KappaIgD/iFLC=0.606,after 4 chemotherapy cycle,KappaIgD/Mprotein= 0.535,KappaIgD/i FLC=0.449,p<0.05.So we considered that the decline of IgD levels,M protein and iFLC levels are consistent,but the consistencyis weak.(5)The median follow-up time was 24.3 months(0.6~103.0 months)in 130 IgD MM patients,and the overall response rate was 82.3%(107/130).Compared different types of MM patients at the same period(2008.01-2015.12),we found that the ORR of IgD MM patients had no difference with IgG and IgA,but CR rate(10.5% VS 12.6% VS 21.8%)and above VGPR remission rate(27.9% VS 41.1% VS 60.4%)worse than IgG and IgA MM,the difference was statistically significant,p<0.05.(6)In the 130 patients with IgD MM,71 had died,92 had progress/relapsed,the median PFS was 19.3 months,and the median OS was 31.1 months.The survival time of patients with IgD MM was significantly shorter than that of IgG MM and IgA MM at the same period,p< 0.0001.(7)Of the 130 patients with IgD type multiple myeloma,22 cases were treated with conventional chemotherapy and 108 cases were treated with bortezomib-based combination chemotherapy.There was no difference in CR rate and VGPR rate between the two groups,but the ORR rate in Bortezomib-based combination chemotherapy group was significantly higher than the traditional chemotherapy group,the ORR rate was 86.1% and 63.6%,respectively,p=0.012.Then we further compared the survival of the two groups found that the median progression-free survival time(PFS)and the median overall survival(OS)time was 19.3 months VS 19.2 months,30.6 months VS 31.1 months in traditional chemotherapy group,based on bortezomib chemotherapy group,respectively.The difference was not statistically significant,p>0.05.(8)In the 130 patients with IgD MM,univariate analysis showed that Hb levels,PLT levels,LDH levels could affect the survival of patients.Multivariate results showed that the level of LDH was independent factors affect PFS and OS in IgD MM patients.The survival time of Ig D MM patients with elevated LDH levels was significantly shorter than normal LDH levels group.The median progression-free survival time(PFS)and the median overall survival(OS)time was 12.5 months VS 21.3 months,21.6 months VS 39.5 months in elevated LDH levels group and normal LDH levels group,p<0.05.Conclusion: IgD MM is a rare type of MM,occurred in a younger age,and has a poor prognosis,λ was the main type of light chain,Ⅲ phase was more common when newly diagnosed.Anemia,renal dysfunction,high calcium,extramedullary plasma cytoma were more outstanding in IgD MM patients,and tumor burden(LDH levels,β2MG levels,plasma cell ratio)is usually higher.In addition,the positive rate of 1q21 amplification and t(11;14)is also higher in IgD MM.Although the use of proteasome inhibitors have improved the the overall response rate in IgD MM,did not extend the survival time of IgD MM patients.The decline of IgD levels,M protein and iFLC levels are consistent,so we recommend combination IgD quantitation detection be applied to evaluation of clinical efficacy in IgD myeloma.LDH is independently adverse factor affecting IgD MM prognosis.