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Kinetics of hematologic response in AL amyloidosis: insights from clinical and cytogenetic subgroup analysis in the daratumumab era

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)...

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Main Authors: Bazarbachi, Abdul Hamid (Author) , Zanwar, Saurabh (Author) , Hegenbart, Ute (Author) , Trajanova, Despina (Author) , Bhutani, Divaya (Author) , Gertz, Morie A. (Author) , Dispenzieri, Angela (Author) , Kumar, Shaji (Author) , D'Souza, Anita (Author) , Patwari, Anannya (Author) , Cowan, Andrew (Author) , Chen, GuiZhen (Author) , Milani, Paolo (Author) , Palladini, Giovanni (Author) , Sanchorawala, Vaishali (Author) , Bodanapu, Geethika (Author) , Mohty, Mohamad (Author) , Lentzsch, Suzanne (Author) , Schönland, Stefan (Author) , Muchtar, Eli (Author) , Chakraborty, Rajshekhar (Author)
Format: Article (Journal)
Language:English
Published: 28 December 2025
In: HemaSphere
Year: 2025, Volume: 9, Issue: 12, Pages: 1-16
ISSN:2572-9241
DOI:10.1002/hem3.70276
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/hem3.70276
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hem3.70276
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Author Notes:Abdul-Hamid Bazarbachi, Saurabh Zanwar, Ute Hegenbart, Despina Trajanova, Divaya Bhutani, Morie A. Gertz, Angela Dispenzieri, Shaji Kumar, Anita D'Souza, Anannya Patwari, Andrew Cowan, GuiZhen Chen, Paolo Milani, Giovanni Palladini, Vaishali Sanchorawala, Geethika Bodanapu, Mohamad Mohty, Suzanne Lentzsch, Stefan O. Schönland, Eli Muchtar, Rajshekhar Chakraborty
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Summary: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.
Item Description:Gesehen am 31.03.2026
Physical Description:Online Resource
ISSN:2572-9241
DOI:10.1002/hem3.70276

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