Clinical Characteristics,Survival Outcomes And Prognosis In 82 Immunoglobulin D Multiple Myeloma Patients

Objective:To analyze the clinical characteristics,survival outcomes and prognosis of 82 immunoglobulin D(IgD)multiple myeloma(MM)patients that received different therapeutic patterns.Methods:82 IgD MM(part of a series of 1635 symptomatic patients with MM,5.0%)treated between March 1995 and December 2017 at the Blood Diseases Hospital of the Chinese Academy of Medical Sciences were included in this study.We undertook retrospective study to analyze these patients’ clinical characteristics,laboratory date and treatment patterns.The Chi-square test,u-test,t-test and Fisher’s exact test were used in the comparison of demographic characteristics.Survival analysis were estimated according to the Kaplan-Meier method.Log-rank test was used to compare the univatiate analysis.We used the Cox proportional hazards regression model to estimate hazard ratios.Results:①The median age was 51 years(29～72 years),male-to-female ratio was 59:23,with preponderance of lambda light chains(87.7%),high prevalence of Bence Jones proteinuria(81.8%vs.66.0%)and low serum M-component(median 10.64 g/L vs.25.14 g/L).Compared with non-IgD myeloma patients,patients with IgD myeloma had higher frequencies of renal failure(38.3%vs.21.4%,p=0.000),bone marrow plasmacytosis>50%(37.1%vs.25.8%.p=0.036),high serum LDH(44.6%vs.11.9%,p=0.000)and extramedullary disease(EMD)(18.2%vs.9.7%.p=0.044).In addition,IgD myeloma was more frequently in patients at R-ISS stage III(39.7%vs.28.5%,p=0.017),cytogenetic abnormalities(31.1%vs.19.6%)and complex karyotype(26.2%vs.15.2%).88%(52/59)of the patients with IgD myeloma had at least one cytogenetic abnormality demonstrated by FISH.The frequencies of 1q21 amplification(81.4%vs.57.3.p=0.000)and t(11;14)(47.5%vs.18.7%,p=0.000)were much higher in IgD patients than other subtypes myeloma.②Among 82 IgD MM patients,31 cases received bortezomib-based treatment,33 with non-bortezomib treatment 18 cases with ASCT.The median OS were 35.3 months,37.6 months and 72.3 months,the difference of OS between bortezomib-based and non-bortezomib group was not statistically significant(P=0.940),but the median OS of ASCT group was significantly better than the other two groups(p<0.05).After ASCT,8 cases received maintenance therapy with thalidomide or lenalidomide(ASCT+tha/len),10 cases received 2-4 cycles bortezomib-based consolidation or second ASCT(2 cases)then followed by thalidomide or lenalidomide(ASCT+bortezomib/ASCT+tha/len),The median OS were 72.3 and non-reached respectively(p=0.413).Under novel therapies,the median OS of patients with IgD and non-IgD myeloma was 56.1 months and 72.2months,respectively(p=0.402),median PFS was 30.6 months and 34.0 months,respectively(p=0.157),there was no statistical difference between the two groups.③In univariate analysis the significant prognostic factors for reduced OS were complex karyotype(≧3),chromosomel3 deletions,renal dysfunction,ISS stage III,R-ISS stage III and whether the patient had received ASCT(p<0.05).Multivariate analysis found R-1SS stage III and chromosomel3 deletions were independent prognostic factor for overall survival.In addition,chromosome 13 deletions was also independent prognostic factor for PFS.Conclusion:our study demonstrated that IgD myeloma is a rare subtype of myeloma(5%),it affects younger patients and frequently presents with a high tumor burden,high frequency of genetic aberrations and features of advanced disease.Under novel therapeutic patterns,the outcome of patients with IgD MM is similar to that of patients with other myeloma subtypes.Bortezomib alone did not bring more survival benefit in IgD myeloma,but ASCT could improve the outcome of IgD myeloma significantly,with a median OS of 72.3 months and a median PFS of 38.9 months.After ASCT,more intensive therapy with second ASCT or bortezomib-based consolidation followed by tha/len might not bring more benefit compared with tha/len only.R-ISS stage III and chromosome13 deletions are independent prognostic factor for survival.In addition,chromosome 13 deletions was also independent prognostic factor for PFS.