Immunoglobulin D (IgD) multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% of cases with limited information is available regarding the prognosis of these isotypes. They have been considered to have a more aggressive course than the more common Immunoglobulin of IgG and IgA isotypes in the era of conventional chemotherapy. Several studies have reported the outcome of IgD MM after autologous hematopoietic stem cell transplantation (ASCT) in recent years, but none in the context of novel agents currently the backbone of almost all if not all lines of therapy upfront.
We sought to study the prognostic impact of novel agents used upfront on IgD MM treated in several IFM (Intergroupe Francophone du Myélome) centres.
This study has included a group of 21 patients with IgD MM that were treated from 1994 to 2012 across 5 IFM centres. IgD MM was diagnosed as outline in international consensus criteria. Response and survival criteria were used as depicted in the IMWG consensus criteria published.
Median age was 59 years (min max 38-80), sex ratio was 1.7, 75% had lambda light chain, 65% had severe bone disease and 20% one to 3 bone lesions, 55% had severe renal insufficiency, 30% had hypercalcemia, 55% profound anemia. Finally, 39% had adverse FISH either del17p or t(4;14) on bone marrow plasma cells and 50% were ISS 3 with beta2M greater than 5mg/L. 80% had receive novel agents containing regimens upfront, including 70% in the context of ASCT and 75% a bortezomib-based regimen.
Overall, 65% reached at least VGPR with a median time to first response at 4 months (IQ 1-5). IgD MM had a greater chance to reach VGPR on bortezomib-based regimen, 80% versus 50% for patients on thalidomide-based regimen; furthermore, ASCT also improved the depth of response rate with 85% versus 20% that reached VGPR, respectively (p=0.022). The presence of renal insufficiency at initiation did not affect the incidence and depth of response rate as expected.
With a median follow-up of 65 months, 40% have relapsed and 35% have died. The median TTP and OS was 3 years (CI95% 3;7) and 6 years (CI95% 5;9), respectively. Although not significant due to the limited number of patients the median OS was much shorter in the group treated with conventional agents as to novel agents, 5 years (2;8) versus not reached with a 6-year event free of 53%. Similarly, the patients that have received a thalidomide-based regimen upfront had a shorter OS as to bortezomib-based regimen, 1.9 years (1;nr) versus 5.8 years (2;9) although not statistically significant. Interestingly, ASCT improved TTP but not OS, with 1.6 years (1;2.5) versus not reached (6-year event free is 63%) as median TTP in patients non ASCT and ASCT, respectively (p=0.045).
Despite the retrospective analysis and the small number of patients, our study showed that the use of ASCT and bortezomib-based regimen improve the prognosis of IgD MM. This data analysis confirms that IgD MM should be treated according to current guidelines upfront that recommend use of a bortezomib-based regimen in the context of ASCT in fit patients. Treatment options including the role of consolidation and maintenance may further improve the outcomes of these patients.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.