The presence of clonal isotype switch after autologous stem cell transplantation as a prognostic biomarker for long-term survival in patients with multiple myeloma

Leuk Res. 2025 Jan 3:149:107641. doi: 10.1016/j.leukres.2025.107641. Online ahead of print.

Abstract

Clonal isotype switch (CIS) in multiple myeloma (MM) refers to the emergence of new immunoglobulin bands distinct from those present at diagnosis. CIS often appears after high-dose chemotherapy and autologous stem cell transplantation (ASCT), reflecting post-transplant immune recovery. However, its prognostic significance remains unclear. In this study, CIS was observed (CIS-positive) in 31.7 % (26/82) of patients undergoing ASCT. Patients receiving bortezomib-containing induction therapy showed a higher prevalence of CIS compared to those treated with vincristine-doxorubicin-dexamethasone chemotherapy (37.9 % vs. 16.7 %, p = 0.061). Median overall survival (OS) was not estimable (NE) in the CIS-positive group, while it was 47 months in the CIS-negative group (hazard ratio [HR]: 0.27, 95 % CI: 0.11-0.67; p = 0.005). Median progression-free survival (PFS) was also NE in the CIS-positive group versus 26 months in the CIS-negative group (HR: 0.25, 95 % CI: 0.11-0.58; p = 0.001). These findings suggest that CIS is an independent biomarker associated with favorable outcomes in MM patients undergoing ASCT.

Keywords: Autologous stem cell transplantation; Clonal isotype switch; Multiple myeloma.