Clinical characteristics and outcomes of IgD myeloma: experience across UK national trials

Abstract

Immunoglobulin D (IgD) myeloma is a subtype often considered to have adverse features and inferior survival, but there is a paucity of data from large clinical studies. We compare the clinical characteristics and outcomes of patients with IgD myeloma from UK phase 3 myeloma trials analyzed in 2 groups: old (1980-2002) and recent (2002-2016) clinical trials, based on the time of adoption of novel myeloma therapies. Patients with IgD myeloma comprised 44 of 2789 (1.6%) and 70 of 5773 (1.2%) of the old and recent trials, respectively. Overall, IgD myeloma was associated with male predominance, low-level paraproteinemia (<10g/L), and λ light chain preference. The frequency of ultra-high-risk cytogenetics was similar in IgD myeloma compared with other subtypes (4.3% vs 5.3%, P > .99). Despite the old trial series being a younger group (median age: 59 vs 63 years, P = .015), there was a higher frequency of bone lesions, advanced stage at diagnosis, worse performance status, and severe renal impairment compared with the recent trials. Furthermore, the early mortality rate was significantly higher for the old trial series (20% vs 4%, P = .01). The overall response rate following induction therapy was significantly higher in the recent trials (89% vs 43%, P < .0001), and this was consistent with improved median overall survival (48 months; 95% confidence interval [CI] 35-67 months vs 22 months; 95% CI, 16-29 months). Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types because of earlier diagnosis, novel therapies, and improved supportive care. This trial was registered at clinicaltrials.gov as # NCT01554852.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract

Figure 1.

Comparison of baseline patient characteristics for the myeloma subsets across UK MRC/NCRI clinical trials. Plt, platelet count; Hb, hemoglobin concentration; PS, performance status; LCO, light chain only myeloma. The box and whisker plot compares the ages of patients with IgD myeloma in the respective trials. Box indicates median and interquartile range; whiskers indicate range.

Figure 2.

Frequency of cytogenetic risk groups and clinical responses for IgD myeloma. (Ai) Cytogenetic risk stratification of participants in the recent UK myeloma clinical trials (Myeloma IX and XI). Graph shows the percentage of the cytogenetic risk groups for the various myeloma subtypes. (Aii) Comparison proportions of the cytogenetic risk groups for IgD myeloma vs other myeloma subtypes. UHiR, ultra high risk; HiR, high risk; SR, standard risk; N/A, not available. (B) Clinical responses following induction therapy based on the IMWG response criteria. CR, complete response; VGPR, very good partial response; PR, partial response; SD; stable disease; PD, persistent disease; N/A, not available.

Figure 3.

Old myeloma trials. (A) Overall survival of patients with myeloma stratified by paraprotein type. (B) Progression-free survival of patients with myeloma stratified by paraprotein type.

Figure 4.

Recent myeloma trials. (A) Kaplan-Meier plot comparing overall survival between IgD myeloma and other subtypes. (B) Kaplan-Meier plot comparing progression-free survival between IgD myeloma and other subtypes. (C) Kaplan-Meier plot of overall survival stratified by paraprotein class. (D) Kaplan-Meier plot of progression-free survival stratified by paraprotein class. (E) Overall survival of patients with IgD myeloma stratified by cytogenetic risk group. (F) Progression-free survival of patients with IgD myeloma stratified by cytogenetic risk group.