ArticleHemaSphere2025
Kinetics of hematologic response in AL amyloidosis: Insights from clinical and cytogenetic subgroup analysis in the daratumumab era.
Article in HemaSphere, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
21 authors.
Funding
Abstract
Rapid and profound reduction of free light chains (FLCs) improves outcomes in AL amyloidosis; however, early FLC kinetics with daratumumab-based frontline therapy remain undefined. We retrospectively analyzed 315 patients treated with daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCd) or Dara-Vd at eight centers. Involved FLC (iFLC), the difference between iFLC and uninvolved FLC (dFLC), and hematologic response (≥very good partial response [VGPR]) were assessed at baseline and at 1, 3, and 6 months, and correlated with light chain isotype, disease burden (bone-marrow plasma-cell percentage [%BMPC], baseline dFLC), and cytogenetics. Hematological ≥VGPR increased from 49.8% at 1 month to 66.0% at 3 months. The kappa isotype showed slower responses, with higher iFLC/dFLC and lower ≥VGPR at each time point compared to lambda. Higher %BMPC or baseline dFLC predicted persistently elevated iFLC/dFLC and reduced ≥VGPR. The t(11;14) translocation was associated with lower baseline FLC but similar subsequent kinetics. BMPC < 10% and dFLC < 18 mg/dL independently predicted early ≥VGPR (in ≤1 month). Early ≥VGPR conferred superior hematologic event-free survival (heme-EFS) and overall survival (OS) versus later responders (P < 0.001). At a 3-month landmark, achieving dFLC < 1 mg/dL further stratified prognosis, conferring longer heme-EFS and OS (P < 0.01). Frontline Dara-based therapy elicits rapid, deep responses in AL amyloidosis; early ≥VGPR (within 1 month) and dFLC < 1 mg/dL by 3 months predict durable EFS and OS, whereas higher baseline disease burden delays hematologic response.
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Registered trials
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