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

Sep 29, 2026

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The chromosomal translocation t(11;14)(q13;q32) is frequently seen in systemic light-chain (AL) amyloidosis, but its clinical meaning under daratumumab-based therapy is uncertain. In a retrospective single-center comparison, 68 AL amyloidosis patients were contrasted with 107 newly diagnosed multiple myeloma patients using the MM cohort as reference. t(11;14) appeared in 55.9% of AL amyloidosis versus 28.0% of MM and defined a distinct light-chain-only and CD20-high phenotype. In AL amyloidosis, renal dysfunction was less common, overall survival was similar, but event-free survival was worse with inferior hematological and cardiac responses, suggesting delayed daratumumab benefit.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Materials and methods

Patients and study design

Baseline characteristics and staging

Clinical and Experimental Medicine (2026) 26:82 [https://doi.org/10.1007/s10238-025-02005-2](https://doi.org/10.1007/s10238-025-02005-2) RESEARCH Clinical significance of t(11;14) translocation in systemic AL amyloidosis in the era of daratumumab therapy Nao Nishimura1 · Yawara Kawano1 · Jun-ichirou Yasunaga1 Received: 12 November 2025 / Accepted: 11 December 2025 © The Author(s) 2025 Abstract 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. Keywords AL amyloidosis · t(11;14) · CD38 · Daratumumab Introduction Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a monoclonal plasma cell disorder in which monoclonal immunoglobulin light-chain-derived amyloid fibrils deposit throughout the body, leading to organ failure. Patients with cardiac involvement in AL amyloidosis have been considered to have poor prognosis, which led to the attempt to develop more effective treatments. The introduction of daratumumab, a CD38 monoclonal antibody, has profoundly impacted the outcomes ofAL amyloidosis patients [1–3] . However, treatments against patients with severe organ disfunctions and patients refractory to daratumumab 􀀍 Yawara Kawano [ykawanomn@kuh.kumamoto-u.ac.jp](ykawanomn@kuh.kumamoto-u.ac.jp) 1 Department of Hematology, Rheumatology, and Infectious Diseases, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860–8556, Japan based therapies are still challenging. Moreover, the biological features of monoclonal plasma cells and the mechanisms underlying the development of AL amyloidosis remain largely unclear. The chromosomal translocation t(11;14)(q13;q32) in bone marrow monoclonal plasma cells (BMPCs), which brings together the immunoglobulin heavy-chain locus and the oncogene cyclin D1, occurs in approximately 40–60% of AL amyloidosis cases [4, 5] and 15–20% of multiple myeloma (MM) cases [6, 7] . Several common features have been reported in t(11;14) positive MM cases such as higher incidences of specific M protein subtypes (light chain only, immunoglobulin (Ig) M, IgE, and non-secretory) [6, 8] and unique surface molecule expression patterns (higher CD20 positivity and decreased CD56 expression) of BMPCs [9] . Furthermore, t(11;14) positivity is generally considered asa standard-risk feature with neutral prognosis in MM [10] while in AL amyloidosis, the presence of t(11;14) is linked to inferior response to bortezomib-based regimens [4, 11] . Although the frequency of t(11;14) positive cases are much higher in AL amyloidosis compa

FAQs

What did the study compare regarding t(11;14) status?

It compared clinical and cytogenetic characteristics between systemic AL amyloidosis patients and newly diagnosed multiple myeloma patients, using the MM cohort as a reference. It also assessed differences in response and survival among AL amyloidosis patients receiving upfront daratumumab-containing regimens.

How common was t(11;14) in AL amyloidosis versus multiple myeloma?

t(11;14) was detected in 55.9% of AL amyloidosis patients and 28.0% of multiple myeloma cases.

Does t(11;14) affect outcomes with daratumumab-containing therapy in AL amyloidosis?

Overall survival did not differ significantly by t(11;14) status, but event-free survival was significantly shorter in the t(11;14)-positive group. The study also observed inferior 3-month hematological and cardiac responses.

Sep 29, 2026

Uploaded by Rhys