Prognostic impact of translocation t(11;14) and of other cytogenetic abnormalities in patients with AL amyloidosis in the era of contemporary therapies

Objectives: Translocation t(11;14) is the most common cytogenetic abnormality in patients with systemic AL amyloidosis with prognostic and therapeutic relevance, which has not been clearly defined in the most recent therapeutic era. Methods: We assessed its prognostic role in 146 newly-diagnosed patients who received novel agent-based treatment combinations. Event-free survival (EFS), a composite endpoint defined by hematological progression, start of a new treatmentline or death, and overall survival (OS) were the primary endpoints. Results: Half of the patients had at least one FISH abnormality; 40% had t(11;14) which was inversely associated with other cytogenetic abnormalities. At 1, 3, and 6-month landmarks, hematologic response rates were numerically but not statistically higher in the non-t(11;14) group. Patients with t(11;14) were more frequently switched to second-line treatment within 12 months (p =.015). At median follow-up of 31.4 months, t(11;14) was associated with shorter EFS [17.1 (95% CI 3.2-10.6) vs. 27.2 months (95% CI 13.8-40.6), p =.021] and retained its prognostic significance in the multivariate model (HR:1.66, p =.029). The effect on OS was neutral, possibly due to the use of effective salvage therapies. Conclusions: Our data support the use of targeted therapies for patients with t(11;14) to avoid delays in the achievement of deep hematologic responses.