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

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.