IgD Myeloma: Clinical Features and Outcome In The Era Of Novel Agents
Authors: Zagouri Flora , Kastritis Efstathios , Symeonidis Argiris S. , Giannakoulas Nikolaos , Katodritou Eirini , Delimpasi Sosana , Repousis Panagiotis , Giannouli Stavroula , Mandala Eudokia M. , Terpos Evangelos , Dimopoulos Meletios A. 
Published: October 2019

Abstract
IgD multiple myeloma is a rare variant of the disease and in various series accounts for about 2% of patients with symptomatic myeloma. It has been suggested that patients with IgD myeloma may have an inferior outcome when compared to other patients. However, data on IgD myeloma patients treated in the novel agent era are lacking. In order to assess the frequency and evaluate the outcome and the specific characteristics of patients with IgD myeloma we analyzed the database of the Greek Myeloma Study Group to identify such patients.
Between January 2000 and December 2012, among the 1239 patients with previously untreated, symptomatic, myeloma, 31 patients (2.5%) were diagnosed with IgD myeloma. Of interest, 84% of patients with IgD myeloma had lambda light chain (versus 38% of the patients with other subtypes of MM, p<0.001). The median age of patients with IgD myeloma was 65 years (range 26-80 years) versus 68 years (range 23-96 years) for patients with other subtypes of MM (p=0.073), while 10% of patients with IgD versus 28% of the other patients were >65 years (p=0.023) and 10% of patients with IgD versus 3.8% of the other patients were ≤40 years of age. Patients with IgD myeloma presented more often with significant renal dysfunction (serum creatinine ≥2 mg/dl in 52% versus in 19%, p<0.001 or eGFR <30 ml/min/1.73m2 in 42% versus 18% in patients of other subtypes, p=0.001) and excreted larger amounts of Bence Jones protein (59% excreted ≥2 gr per day versus 17% of the other patients, p<0.001). Patients with IgD myeloma had also more often features of high risk disease including ISS-3 disease (60% versus 37% for the other patients, p=0.011) and elevated serum LDH (≥300 IU/L) in 29% versus10% of the other patients (p=0.001).
Response to primary therapy for patients with IgD myeloma was similar to other patients (at least PR in 77% versus 72% respectively), although there was a trend for better quality of responses in patients with IgD myeloma (sCR and CR in 26% versus 15% of patients, and at least VGPR in 53% versus 29% in patients of other subtypes, respectively, p=0.059). However, more patients with IgD myeloma had received primary therapy with bortezomib-based regimens (40% versus 22%) and less often IMiD-based therapy (20% versus 35%), while similar proportions of patients received conventional chemotherapy-based regimens (40% versus 44%; p=0.043). Despite the increased frequency of features of high risk disease in patients with IgD myeloma, the median survival of these patients was 51.5 months versus 50.7 months for patients of other subtypes (p=0.850). In a multivariate model to adjust for differences in prognostic features, IgD myeloma was not associated with a different prognosis. We also compared the outcome of patients with IgD myeloma treated before and after January 1st, 2000. The survival of the patients with IgD myeloma who started therapy before versus after 2000 was 44 months (p=0.018).
In conclusion, in a large series of patients with symptomatic multiple myeloma, the incidence of IgD myeloma is 2.5%. The vast majority of patients with IgD myeloma is associated with lambda light chain and present more often with significant Bence Jones proteinuria, significant renal dysfunction and features of advanced disease. However, their outcome in the era of novel agents is similar to that of patients with other myeloma subtypes.

Disclosures:
No relevant conflicts of interest to declare.