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A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dex...

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Detalles Bibliográficos
Autores principales: Dispenzieri, Angela, Kastritis, Efstathios, Wechalekar, Ashutosh D., Schönland, Stefan O., Kim, Kihyun, Sanchorawala, Vaishali, Landau, Heather J., Kwok, Fiona, Suzuki, Kenshi, Comenzo, Raymond L., Berg, Deborah, Liu, Guohui, Kumar, Arun, Faller, Douglas V., Merlini, Giampaolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727292/
https://www.ncbi.nlm.nih.gov/pubmed/34168284
http://dx.doi.org/10.1038/s41375-021-01317-y
Descripción
Sumario:In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1–2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician’s choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib–dexamethasone vs 51% with physician’s choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32–0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib–dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options.