Prognostic impact of cytogenetic abnormalities detected by FISH in AL amyloidosis with daratumumab-based frontline therapy
We performed an international retrospective study on 283 patients with light chain (AL) amyloidosis to investigate the prognostic impact of cytogenetic abnormalities by fluorescence in situ hybridization, when treated with frontline daratumumab-based therapy. The cytogenetic subgroups of interest we...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 December 2024
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| In: |
Blood
Year: 2024, Volume: 144, Issue: 25, Pages: 2613-2624 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.2024025899 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2024025899 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497124023164?pes=vor&utm_source=clarivate&getft_integrator=clarivate 
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| Author Notes: | Rajshekhar Chakraborty, Saurabh Zanwar, Ute Hegenbart, 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, Stefan O. Schoenland, Suzanne Lentzsch and Eli Muchtar |
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| 245 | 1 | 0 | |a Prognostic impact of cytogenetic abnormalities detected by FISH in AL amyloidosis with daratumumab-based frontline therapy |c Rajshekhar Chakraborty, Saurabh Zanwar, Ute Hegenbart, 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, Stefan O. Schoenland, Suzanne Lentzsch and Eli Muchtar |
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| 520 | |a We performed an international retrospective study on 283 patients with light chain (AL) amyloidosis to investigate the prognostic impact of cytogenetic abnormalities by fluorescence in situ hybridization, when treated with frontline daratumumab-based therapy. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) (hereafter, +1q), hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t [14;20]). The end points of interest were rate of hematologic complete response (heme-CR), very good partial response (VGPR) or better, and hematologic event-free survival (heme-EFS). The incidence of abnormalities was as follows: t(11;14), 53.4%; deletion (13q), 28.9%; +1q, 22.3%; hyperdiploidy, 19.4%; HR translocations, 6.6%; and deletion(17p), 4.5%. The heme-CR rate by cytogenetic subgroups were as follows: t(11;14) vs no t(11;14), 45.2% vs 41.8% (P=0.597); del(13q) vs no del(13q), 46.8% vs 42.8% (P=0.594); +1q vs no +1q, 30.2% vs 47.9% (P=0.022); hyperdiploidy vs no hyperdiploidy, 39.5% vs 44.9% (P=0.541); HR translocations vs none, 45.5% vs 43.1% (P=0.877); and del(17p) vs no del(17p), 50.0% vs 42.9% (P=0.658), respectively. Similarly, +1q was the only subgroup with a significantly lower VGPR or better rate (64.2% vs 79.0%; P=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year overall survival (OS) was 80.98% (95% CI, 75.6-85.4). The presence of +1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06,95% CI, 1.14-3.71; P=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme-EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel frontline immunotherapies should be enriched in +1q to further improve outcomes in this subgroup. | ||
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| 650 | 4 | |a DEFINITION | |
| 650 | 4 | |a LIGHT-CHAIN AMYLOIDOSIS | |
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