Key result
The AL-ISS GLS cutoff of 9% did not independently predict overall survival, whereas LVEF <50% (HR 3.18; p=0.006) and dFLC ≥180 mg/L (HR 3.26; p=0.003) were independent predictors.
Why the study?
The prognostic relevance of the AL International Staging System (AL-ISS), which uses echocardiographic GLS to subdivide stage IIIb AL amyloidosis, remains uncertain in the daratumumab era.
Does the AL-ISS GLS cutoff of 9% predict overall survival in newly diagnosed stage IIIb AL amyloidosis in the daratumumab era?
Cohort (n=53)
Does the AL-ISS GLS cutoff of 9% predict overall survival in newly diagnosed stage IIIb AL amyloidosis in the daratumumab era?
In the daratumumab era, the proposed AL-ISS GLS cutoff of 9% does not independently predict overall survival in advanced cardiac AL amyloidosis, whereas LVEF and dFLC remain prognostic.
Prioritize LVEF and dFLC over GLS for prognostication in daratumumab-treated stage IIIb AL amyloidosis; challenges GLS incorporation into AL-ISS.
Survival in AL amyloidosis is strongly influenced by the severity of cardiac involvement. The recently proposed AL International Staging System (AL-ISS) incorporates echocardiographic global longitudinal strain (GLS) to subdivide biomarker-defined stage IIIb disease into stages IIIb and IIIc; however, its prognostic relevance in the daratumumab era remains uncertain. We evaluated the AL-ISS GLS cutoff of 9% in 53 patients with newly diagnosed stage IIIb AL amyloidosis. Patients classified as proposed stage IIIc (GLS 0-9%) had higher baseline difference between involved and uninvolved free light chains (dFLC; 300 vs 167 mg/L; p=0.08), similar left ventricular wall thickness (14.5 vs 15.0 mm; p=0.57), and lower left ventricular ejection fraction (LVEF; 45% vs 55%; p=0.02) compared with those with GLS >9%. GLS correlated moderately with LVEF (ρ=0.47; p<0.001). On multivariable analysis, LVEF <50% (HR 3.18; p=0.006) and dFLC ≥180 mg/L (HR 3.26; p=0.003) independently predicted overall survival, whereas GLS did not. Median overall survival was longer in proposed stage IIIc disease (31 vs 13 months), reflecting greater use of daratumumab-based therapy (82% vs 25%). Among daratumumab-treated patients, survival did not differ by GLS category. These findings suggest limitations of GLS-based sub-staging in advanced cardiac AL amyloidosis in the daratumumab era.
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Berumen et al. (2026) conducted a cohort in newly diagnosed stage IIIb AL amyloidosis (n=53). AL-ISS GLS cutoff of 9% vs. GLS >9% was evaluated on overall survival. The AL-ISS GLS cutoff of 9% did not independently predict overall survival, whereas LVEF <50% (HR 3.18; p=0.006) and dFLC ≥180 mg/L (HR 3.26; p=0.003) were independent predictors.
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