Distinct Clinical Features of Multiple Myeloma With t(11;14): A Post Hoc Analysis of JSH‐MM‐15 Study

Abstract

ABSTRACT t(11;14) (q13;q32) occurs in approximately 15%–25% of multiple myeloma (MM) cases and has traditionally been regarded as a standard cytogenetic risk factor. However, recent evidence suggests that MM with t(11;14) exhibits heterogeneous biological characteristics and clinical outcomes distinct from those associated with other cytogenetic risk categories. In a post hoc analysis of the prospective JSH‐MM‐15 study, we investigated the prognosis of newly diagnosed MM patients to identify prognostic features unique to t(11;14)‐positive cases and to evaluate treatment factors influencing outcomes. Among 482 patients evaluated for t(11;14), 131 (27%) were positive. Overall survival (OS) in t(11;14)‐positive patients was intermediate between standard‐ and high‐risk groups, whereas progression‐free survival (PFS) was comparable to that of high‐risk cases. Deep response rates, including ≥ complete response (CR)/stringent CR and ≥ very good partial response, were lower in t(11;14)‐positive MM than in other risk groups, and these responses were not associated with survival in t(11;14)‐positive cases, in contrast to t(11;14)‐negative MM. Compared with t(11;14)‐negative MM, t(11;14)‐positive patients more frequently expressed CD20 and less frequently expressed CD56 on myeloma cells. Exploratory analyses showed that, despite higher ≥ CR rates, OS was worse in patients with CD20‐negative/CD56‐negative tumors among t(11;14)‐positive MM. Among CD20‐positive patients, PI‐containing regimens were associated with better OS, although no significant PFS benefit was observed. These findings support the biological and clinical heterogeneity of t(11;14)‐positive MM and highlight the need for prospective validation of subgroup‐specific treatment outcomes.