Clinical significance of t(11;14) translocation in systemic AL amyloidosis in the era of daratumumab therapy

The chromosomal translocation t(11;14)(q13;q32) is frequently observed in systemic light-chain (AL) amyloidosis, yet its clinical significance in the era of daratumumab-based therapy remains unclear. To compare clinical and cytogenetic characteristics, we retrospectively analyzed 68 patients with systemic AL amyloidosis and 107 patients with multiple myeloma (MM) newly diagnosed at Kumamoto University Hospital, with the MM cohort serving as a reference cohort. t(11;14) was detected in 55.9% of AL amyloidosis and 28.0% of MM cases. In both diseases, t(11;14) was associated with light chain-only M-protein and elevated CD20 expression on bone marrow plasma cells, suggesting a distinct phenotype. Notably, t(11;14)-positive AL amyloidosis patients exhibited a significantly lower incidence of renal dysfunction, a feature not observed in t(11;14)-positive MM. Among 47 AL amyloidosis patients treated with upfront daratumumab-containing regimens, overall survival did not differ significantly by t(11;14) status. However, event-free survival was significantly shorter in the t(11;14)-positive group (median 41.6 vs. 71.3 months, p = 0.037), accompanied by inferior 3 months hematological and cardiac responses. These findings suggest that t(11;14)-positive AL amyloidosis constitutes a distinct biological and clinical subtype characterized by delayed treatment response to daratumumab. Tailored therapeutic strategies targeting the unique biology of t(11;14)-positive AL amyloidosis is warranted.