Clinical Significance of Immunoglobulin Isotype Switching in Patients with Multiple Myeloma

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. However, immunoglobulin isotype switching (IS) has been reported during follow-up of patients with MM. Its clinical significance has not been established well. We aimed to evaluate the clinical characteristics of the patients with IS and outcomes in those patients in a single center cohort.

A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and June 2012. We compared clinical characteristics and outcomes between those with and without IS.

Of the 377 patients, 34 (9%) demonstrated IS after a median 7. 9 months (range, 2. 2–95. 7 months) from diagnosis. These 34 patients with IS comprised 18. 2% (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3. 1% (7/229) of patients treated without ASCT (P<0. 001). Original immunological types were as follows: IgG (n=10), IgA (n=8), IgD (n=5), free kappa (n=4), and free lambda (n=7). Nine patients among them demonstrated second IS during follow-up. With a median follow-up times of 54. 1 months from the day of diagnosis in all study patients, the median OS has not been reached in patients with IS, and was 38. 3 months in patients with the absence of IS (P<0. 001). Multivariate analysis indicated that development of IS was a significantly favorable prognostic factor for predicting OS (Hazard ratio = 0. 19; 95% confidence interval = 0. 07–0. 53). ECOG PS 0–1 vs. 2–4, creatinine <2 mg/dL vs. ≥2 mg/dL, bone marrow plasma cells <50% vs. ≥50%, and ASCT done vs. not done were also independent prognostic factors for OS (P=0. 037, P<0. 001, P=0. 008 and P<0. 001, respectively). In the group of patients presenting with IS (n=34), differences in overall survival (OS) were not observed according to the timing of IS after diagnosis (<8 mo vs. ≥8 mo, P=0. 836), immunoglobulin isotypes (P=0. 176) and presence of second IS (P=0. 494), while ASCT was associated with longer survival (median OS; not reached vs. 65. 9 mo, P=0. 018).

We confirmed higher frequency of IS in those who underwent ASCT and favorable prognosis in those experiencing IS. Its significance and underlying mechanism warrants further investigation.

No relevant conflicts of interest to declare.