Poor outcomes of immunoglobulin D multiple myeloma patients in the era of novel agents: a single‐center experience
2019; Wiley; Volume: 39; Issue: 1 Linguagem: Inglês
10.1186/s40880-019-0395-3
ISSN2523-3548
AutoresQian Zhao, Feng Li, Ping Song, Xiaogang Zhou, Zhi-Ming An, Jian-Gang Mei, Jingjing Shao, Hanqing Li, Xiuli Wang, Xing Guo, Yong‐Ping Zhai,
Tópico(s)Amyloidosis: Diagnosis, Treatment, Outcomes
ResumoCancer CommunicationsVolume 39, Issue 1 51 p. 1-6 Letter to the Editor Open Access Poor outcomes of immunoglobulin D multiple myeloma patients in the era of novel agents: a single-center experience Qian Zhao, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Qian Zhao and Feng Li contributed equally to this workSearch for more papers by this authorFeng Li, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Qian Zhao and Feng Li contributed equally to this workSearch for more papers by this authorPing Song, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXiaogang Zhou, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorZhiming An, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorJiangang Mei, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorJingjing Shao, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorHanqing Li, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXuli Wang, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXing Guo, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorYongping Zhai, Corresponding Author zhaiyongping00@163.com Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Correspondence: zhaiyongping00@163.comSearch for more papers by this author Qian Zhao, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Qian Zhao and Feng Li contributed equally to this workSearch for more papers by this authorFeng Li, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Qian Zhao and Feng Li contributed equally to this workSearch for more papers by this authorPing Song, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXiaogang Zhou, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorZhiming An, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorJiangang Mei, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorJingjing Shao, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorHanqing Li, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXuli Wang, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorXing Guo, Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. ChinaSearch for more papers by this authorYongping Zhai, Corresponding Author zhaiyongping00@163.com Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Xuanwu District, Nanjing, 210002 Jiangsu, P. R. China Correspondence: zhaiyongping00@163.comSearch for more papers by this author First published: 27 September 2019 https://doi.org/10.1186/s40880-019-0395-3Citations: 1 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Dear Editor, Multiple myeloma (MM) is a disease characterized by the clonal expansion of malignant plasma cells in the marrow, leading to anemia, hypercalcemia, bone lesion, and renal dysfunction [1]. Immunoglobulin D (IgD) myeloma is a rare subtype of MM, accounting for approximately 1% to 2% of all MM patients [2]. It occurs at a young age, often accompanied with a high disease burden and short median survival (18–21 months) [3, 4]. Several studies have suggested that in patients with IgD subtype, the outcomes of those who have had undergone autologous stem cell transplantation (ASCT) were superior than those treated with chemotherapy alone [5, 6]. However, these have been debatable as other reports have displayed opposite results [7, 8]. In the last decade, novel agents such as proteasome inhibitor and immunomodulatory agents have been used to treat MM, which have resulted in a 50% improvement in the patients’ overall survival (OS: 44.8 vs. 29.9 months) [9]. However, given the rarity of IgD myeloma, studies on it remain rare. Knowledge about this subtype was mostly derived from few single-center case series. In China, there has been no report to fully elucidate on whether the results of survival outcomes for patients with IgD subtype from novel agents could be replicated in those with non-IgD subtypes. Here, we performed a retrospective analysis on 216 symptomatic MM patients, diagnosed from August 2006 to April 2018, at the Jinling Hospital (Nanjing, Jiangsu, China). The patient cohort comprised of 13 with IgD subtype and 203 with non-IgD subtypes. Three new drugs, bortezomib, thalidomide, and lenalidomide, were used as induction therapy choice, based on which we investigated their clinical manifestations, treatment responses, and outcomes. In this study cohort, 1 patient with IgD subtype and 11 with non-IgD subtypes underwent ASCT. First, we compared the clinical features between the IgD and non-IgD subtypes (Table 1). The median age of onset for the IgD subtype was 52 years, which was younger than that of the non-IgD subtypes (60 years, P = 0.028). The rate of λ light chain was significantly higher in patients with the IgD subtype than in those with non-IgD subtypes (92.3% vs. 48.8%, P = 0.006). Moreover, as compared with non-IgD subtypes, patients with IgD subtype presented more often with significant renal dysfunction (creatinine > 2 mg/L, P < 0.001) and amyloid light-chain (AL) amyloidosis (P = 0.001) and had higher frequencies of critical clinical features such as International staging system (ISS)-III disease (P = 0.002), severe anemia (Hemoglobin < 90 g/L, P = 0.011), high β2 microglobulin (β2Μ) concentration (P = 0.001), and elevated lactate dehydrogenase (LDH > 250 U/L, P = 0.002). However, there were no significant differences in sex, platelet counts, bone lesion, hypercalcemia, urine protein, induction therapy, and extramedullary infiltration between IgD and non-IgD subtypes. Table 1. Clinical characteristics and treatment of 216 patients with multiple myeloma Characteristics IgD subtype Non-IgD subtypes P value Cases, n 13 203 Age [years; median (range)] 52 (44–66) 60 (24–82) 0.028 Sex [cases (%)] 0.782 Male 8 (61.5) 117 (57.3) Female 5 (38.5) 86 (42.7) Hemoglobin [g/L; mean (range)] 73 (44–108) 90 (40–107) 0.011 Platelets < 100 × 109/L [cases (%)] 4 (30.8) 32 (15.8) 0.306 Light chain type [cases (%)] 0.006 κ 1 (7.7) 104 (51.2) λ 12 (92.3) 99 (48.8) Creatinine > 2 mg/dL [cases (%)] 9 (69.2) 47 (23.2) < 0.001 β2M [mg/L; mean (range)] 10 (2.57–16.50) 5.16 (1.45–19.40) 0.001 Bone lesion [cases (%)] 10 (76.9) 170 (83.7) 0.459 Hypercalcemia [cases (%)] 3(23.1) 14 (6.9) 0.117 Urine protein (g/L) 3.20 (0.15–19.69) 1.30 (0.10–26.10) 0.196 LDH > 250 U/L [cases (%)] 7 (53.8) 37 (18.2) 0.002 ISS stage [cases (%)] 0.002 I 0 41 (20.2) II 0 58 (28.6) III 13 (100.0) 104 (50.2) Induction therapy [cases (%)] 0.080 IMiD-based regimens 4 (30.8) 121(59.6) Bortezomib-based regimens 9 (69.2) 82 (40.4) Final response [cases (%)] 0.847 sCR, CR 4 (30.8) 68 (33.5) VGPR 3 (23.1) 80 (39.4) PR 4 (30.8) 43 (20.9) SD plus PD 2 (15.4) 12 (5.8) AL amyloidosis [cases (%)] 4 (30.8) 8 (3.9) 0.001 Extramedullary infiltration [cases (%)] 2 (15.4) 57 (28.1) 0.500 IgD immunoglobulin D, β2M β2 microglobulin, LDH lactate dehydrogenase, ISS international staging system, IMiD immunomodulatory drug, sCR strict complete response, CR complete response, VGPR very good partial response, PR partial response, SD stable disease, PD progressive disease, AL amyloidosis amyloid light-chain amyloidosis Based on the data from Table 2, we found that 30.8% (4/13) of patients with IgD subtype presented with significant abnormalities in serum-free light chain (sFLC) ratio (< 0.01 or > 100) at baseline, compared with 7.5% (13/173) for the non-IgD subtypes (P= 0.021). Moreover, about half of those (46.2%) with IgD subtype showed an obvious increase in sFLC ratio abnormalities when relapsed (P< 0.001). Table 2. The sFLC concentrations and abnormal ratios of the investigated 186 patients Variable Baseline After relapse IgD subtype (n = 13) Non-IgD subtypes (n= 173)a P value IgD subtype (n= 13) Non-IgD subtypes (n= 96) P value sFLC [mg/L; median (range)] κ 12.10 (8.54–186.40) 25.80 (1.49–17,780.00) 0.567 15.60 (8.50–1708.00) 56.00 (7.49–4541.00) 0.655 λ 129.70 (8.46–4303.00) 28.80 (1.33–17,600.00) 0.151 583.86 (10.51–1092.00) 687.00 (1.33–4000.00) 0.412 κ/λ < 0.01 or > 100 [cases (%)] 4 (30.78) 13 (7.51) 0.021 6 (46.15) 7 (7.29) < 0.001 sFLC serum free light chain, IgD immunoglobulin D a Serum-free light chains were only available for 173 cases of MM patients at the time of diagnosis Of the 216 MM patients, 198 (91.7%) were subjected to cytogenetic abnormality testing (Table 3). 1q21 amplification was discovered in 9 patients with IgD subtype, which was higher than that in patients with non-IgD subtypes (75.0% vs. 40.3%, P= 0.018). The rate of t (14;16) was also significantly higher in patients with IgD subtype than those with the non-IgD subtypes (17.0% vs. 1.6%, P= 0.023). However, no significant differences in other cytogenetic abnormalities such as 13 deletions, t (4;14), t (11;14), p53 deletion, and hyperdiploid between the IgD and non-IgD subtypes were found. Table 3. Abnormal cytogenetic characteristics in 198 case of MM patients Variable IgD subtype [cases (%)] Non-IgD subtypes [cases (%)] P value Total 12 186 13 deletion 4 (33.3) 59 (31.7) 0.907 1q21 amplification 9 (75.0) 75 (40.3) 0.018 IGH rearrangement 6 (50.0) 59 (31.7) 0.191 t(4;14) 3 (25.0) 31 (16.7) 0.729 t(11;14) 1 (8.0) 25 (13.4) 0.866 t(14;16) 2 (17.0) 3 (1.6) 0.023 p53 deletion 0 (0) 7 (3.8) 1.000 Hyperdiploid 4 (33.3) 71 (38.2) 0.948 IgD immunoglobulin D, IGH immunoglobulin heavy chain gene Second, we analyzed the treatment response between the IgD and non-IgD subtypes and have listed their detailed information regarding the treatment and survival of the patients with IgD subtype in Table 4. By the end of follow-up on August 31, 2018, 71 deaths were recorded of whom 9 cases (69.2%) were from patients having the IgD subtype. The overall response rate of the entire cohort was 93.5% (202/216). Response of induction therapy for the IgD subtype was similar to that of the non-IgD subtypes (P= 0.847, Table 1). However, the median duration of response in patients with IgD subtype was 10 months, which was significantly shorter than that of patients with non-IgD subtypes (23.6 months, P= 0.002) (Fig. 1a). The median follow-up of the 216 patients was 32.4 months (range 0.96–147 months). In patients with IgD subtype, the median progression-free survival (PFS) was 10.0 months and the median OS was 22.9 months, compared with 27.9 months (P= 0.003; Fig. 1b) and 81.7 months (P< 0.001; Fig. 1c) for patients bearing the non-IgD subtypes. Figure 1Open in figure viewer a Duration of response in patients with IgD subtype or non-IgD subtypes of multiple myeloma, b Kaplan–Meier progression-free survival curves of patients with IgD subtype or non-IgD subtypes of multiple myeloma, c Kaplan–Meier overall survival curves of patients with IgD subtype or non-IgD subtypes of multiple myeloma Table 4. Treatment and survival of the 13 patients with IgD subtype MM Patient no. ISS stage Sex Age (years) Introduction therapy/cycles Response Therapy after PD/cycles Survival status PFS (months) OS (months) 1 III Male 51 CTD/5 CR RAD/6 Alive 6.0 17.6 2 III Female 53 CTD/7 PR RD/8 Alive 8.0 19.5 3 III Male 64 VCD/1 PD NA Dead 0.7 0.9 4 III Male 48 VTD/8 PR RCD Dead 26.2 44.3 5 III Female 59 VTD/2 SD NA Dead 5.1 5.7 6 III Male 44 VCD/9 CR TAD/6 + RAD/6 Alive 42.3 47.0 7 III Female 49 VTD/9 CR RAD/10 Dead 28.0 42.6 8 III Male 52 VCD/9 VGPR RD/6 Dead 8.5 13.0 9 III Male 45 VCD/2 CR CTD/8 Alive 2.4 9.2 10 III Male 59 VD/4 PR VCTD/5 Dead 16.7 16.7 11 III Male 51 CTD/5 PR RAD/3 Dead 10.0 6.6 12 III Female 56 VCD/4 + ASCT VGPR CTD/4 Dead 18.7 22.9 13 III Female 66 VD/4 VGPR RD/6 Dead 48.0 66.0 IgD immunoglobulin D, ISS international staging system, PD progressive disease, PFS progression-free survival, OS overall survival, CTD thalidomide + cyclophosphamide + dexamethasone, CR complete response, RAD lenalidomide + adriamycin + dexamethasone, PR partial response, RD lenalidomide + dexamethasone, VCD bortezomib + cyclophosphamide + dexamethasone, PD progressive disease, NA not applicable, VTD bortezomib + thalidomide + dexamethasone, RCD lenalidomide + cyclophosphamide + dexamethasone, SD stable disease, TAD thalidomide + adriamycin + dexamethasone, VGPR very good partial response, VD bortezomib + dexamethasone, VCTD bortezomib + thalidomide + cyclophosphamide + dexamethasone, ASCT autologous stem cell transplantation Lastly, we analyzed the other risk factors that might have affected the prognoses of the investigated MM patients (Additional file 1: Table S1). Univariate analyses showed that, besides the IgD subtype, patients with high β2M level, elevated LDH level, having extramedullary infiltration, ISS stage III, 13q deletion, 1q21 amplification, IGH rearrangement, and abnormal sFLC ratio had shorter OS compared with their counterparts (Additional file 2: Figure S1). Multivariate analyses showed that IgD subtype was an independent adverse factor for both PFS (P= 0.009) and OS (P= 0.001) (Table 5). Table 5. Multivariate analysis for PFS and OS of 216 patients with multiple myeloma Variable PFS OS HR 95% CI P value HR 95% CI P value LDH > 250 U/L 1.494 1.020–2.189 0.039 2.791 1.692–4.604 < 0.001 ISS stage III 1.298 1.032–1.633 0.026 1.533 1.096–2.145 0.013 IgD subtype 2.221 1.221–4.040 0.009 3.506 1.687–7.285 0.001 1q21 amplification – – – 1.949 1.179–3.224 0.009 IGH rearrangement 1.615 1.260–2.071 < 0.001 1.485 1.165–1.895 0.001 Extramedullary infiltration 2.084 1.421–3.055 < 0.001 3.692 2.199–6.200 < 0.001 PFS progression-free survival, OS overall survival, HR hazard ratio, CI confidence interval, LDH lactate dehydrogenase, ISS international staging system, IgD immunoglobulin D, IGH immunoglobulin heavy chain gene The synthesis rate of IgD is very low in patients bearing the IgD subtype, which often leads to missed diagnosis [2]. Among the 216 MM patients, 13 had IgD subtype (6%). This proportion was similar to another report in China (5.4%) [8] but was slightly higher than that observed in western countries (1%–2%) [2]. Nevertheless, the proportion of IgD subtype may still be underestimated, therefore, identifying and understanding this disease is extremely essential. It has been reported that the IgD subtype of MM occurred more often in young patients, with a median age of 52 to 60 years. Moreover, it was found to be associated with higher β2M, extramedullary involvement, secondary systemic amyloidosis, a λ light chain bias (IgD myeloma is characterized by the presence of a predominance of λ over K light chain type), renal failure, and short survival [3]. The clinical characteristics of our patients were similar to the results of the above-mentioned studies. In addition, we interestingly found that patients with the IgD subtype demonstrated significant sFLC ratio abnormalities at baseline and during disease relapse, especially in the 46.2% of patients with disease relapse. This finding may be conducive to assess the disease progression and to identify early relapse for timely intervention. Moreover, as compared to the IgD subtype patients with abnormal sFLC ratio, those with normal sFLC ratio had a numerically superior OS (42.56 months vs. 5.7 months, P= 0.057, Additional file 3: Figure S2). There was noted solely as a tendency, which may have been most likely due to the small cohort size. High-risk cytogenetic abnormalities in MM patients with IgD subtype have been reported to range from 30 to 50%. In our study, 1q21 amplification was observed in 75% of patients with IgD subtype. It was reported that the overexpression of genes mapping to 1q21 could regulate the growth and resistance of MM to drugs, and result in increasing risk of early death of the patients [10]. Recent research has also found that the adverse effects due to 1q21 amplification on prognosis persisted even after removal of other identified high-risk cytogenetic changes, including p53 deletion, t(4;14), t(14;16), and t(14;20) [11]. Therefore, the association of IgD MM with a high rate of 1q21 amplification might contribute to poor outcomes. Perhaps it could also explain why patients with IgD subtype and non-IgD subtypes had similar response rates, but different duration of response. Researchers have tried different ways to improve the prognosis of patients with IgD subtype all along. In 2005, Wechalekar et al. [5] suggested that the mean OS of IgD subtype patients could be prolonged after ASCT when compared with chemotherapy (5.1 years vs. 2 years, respectively, P = 0.090). In 2014, Zagouri et al. [12] reported a median OS of 51.5 months in 31 IgD subtype patients in Greece, which was the longest survival treated with chemotherapy reported until now. However, in Asia, the data seemed less consistent. In 2008 and 2010, two studies from Korea reported poor outcomes for the IgD subtype patients following ASCT or conventional chemotherapy, with the median OS of 12 and 18.5 months [4, 7]. In 2015, a report from China showed that the median OS and PFS of IgD subtype were 24 and 15.5 months, respectively and no difference in OS was found among the bortezomib-only group, the non-bortezomib group, and the bortezomib + ASCT group [8]. Here, our patients with IgD subtype showed similar median OS (22.9 months) and PFS (10 months) as to these studies from Asia. Though patients with non-IgD subtypes had a favourable median OS of 81.7 months in our study, in the era of novel agents, the survival of patients with IgD subtype still cannot be improved from the new drugs, unlike the non-IgD subtypes. Recently, a case report on a patient with IgD subtype who was refractory to at least 5 different chemotherapy regimens had shown very good partial response to daratumumab (anti-CD38 monoclonal antibody) [13]. We expect that additional agents with novel mechanism including histone deacetylation, target of surface receptors, and chimeric antigen receptor T Cell immunotherapy would improve the survival of IgD subtype patients. In summary, the IgD subtype was found to be an independent adverse risk factor for prognosis. MM patients with IgD subtype presented with a more aggressive disease course and had shorter survival with chemotherapy as compared to the non-IgD subtypes, even in this era of novel agents. Considering the rarity of this subtype, international collaborative studies are suggested to confirm our findings and further elucidate the underlying mechanisms for developing potent therapeutic approaches. Abbreviations ASCT autologous stem cell transplantation AL amyloidosis amyloid light-chain amyloidosis β2M high β2 microglobulin CR complete response CI confidence interval HR hazard ratio IgD MM immunoglobulin D multiple myeloma IGH immunoglobulin heavy chain gene IMiD immunomodulatory drug ISS international staging system LDH lactate dehydrogenase OS overall survival PD progressive disease PFS progression-free survival PR partial response sFLC serum-free light chain sCR strict complete response SD stable disease VGPR very good partial response Acknowledgements We would like to thank all the doctors and nurses of Jinling Hospital, and in particular many colleagues for referring and providing clinical data. We would like to thank all patients participated in this study and who attend our center. Authors’ contributions QZ and FL analyzed the data and prepared the paper. YPZ designed the research and checked the data. PS, XGZ, ZMA, XLW, and XG provided the clinical data and were responsible for the data interpretation. JGM, HQL, and JJS conformed the diagnosis and cytogenetics data and were responsible for reviewing the manuscript. All authors read and approved the final manuscript. Funding Not applicable. Availability of data and materials The dataset used or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the Clinical Research Ethics Committee of Jinling Hospital, Nanjing, China. Written informed consent was waived by the ethics committee. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Supplementary information Supplementary information accompanies this paper at https://doi.org/10.1186/s40880-019-0395-3. Supporting Information Filename Description cac2s4088001903953-sup-0001.docxapplication/docx, 12.9 KB Additional file 1: Table S1. Univariate analysis for PFS and OS of 216 patients with multiple myeloma. cac2s4088001903953-sup-0002.jpgapplication/jpg, 641.5 KB Additional file 2: Figure S1. Kaplan–Meier overall survival curves of patients with multiple myeloma. a: Survival curves of patients stratified according to β2M, ≤ 5.5 mg/L vs. > 5.5 mg/L (P= 0.002); b: Survival of patients according to LDH, ≤ 250U/L vs. > 250U/L (P< 0.001); c: Survival of patients with and without extramedullary infiltration (P < 0.000); d: Survival of patients with and without ISS stage III (P= 0.028); e: Survival of patients with and without 13q deletion (P= 0.003); f: Survival of patients with and without 1q21 amplification (P< 0.000); g: Survival of patients with and without different IGH rearrangement [non-IGH rearrangement vs. t(4;14) vs. t(11;14) vs. t(14;16), P< 0.000]; h: Survival of patients with and without abnormal sFLC ratios (P= 0.035). cac2s4088001903953-sup-0003.jpgapplication/jpg, 454.4 KB Additional file 3: Figure S2. Overall survival in IgD myeloma patients with and without abnormal sFLC ratio. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011; 364 11: 1046– 1060. 10.1056/NEJMra1011442 Crossref CAS PubMed Web of Science®Google Scholar 2Pandey S, Kyle RA. Unusual myelomas: a review of IgD and IgE variants. Oncology. 2013; 27 8: 798– 803. PubMed Web of Science®Google Scholar 3Jancelewicz Z, Takatsuki K, Sugai S, Pruzanski W. IgD multiple myeloma: review of 133 cases. Arch Intern Med. 1975; 135 1: 87– 93. 10.1001/archinte.1975.00330010089012 Crossref CAS PubMed Web of Science®Google Scholar 4Kim MK, Suh C, Lee DH, Min C-K, Kim SJ, Kim K, et al. Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients. 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