TY - JOUR
T1 - A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis
AU - Dispenzieri, Angela
AU - Kastritis, Efstathios
AU - Wechalekar, Ashutosh D.
AU - Schönland, Stefan O.
AU - Kim, Kihyun
AU - Sanchorawala, Vaishali
AU - Landau, Heather J.
AU - Kwok, Fiona
AU - Suzuki, Kenshi
AU - Comenzo, Raymond L.
AU - Berg, Deborah
AU - Liu, Guohui
AU - Kumar, Arun
AU - Faller, Douglas V.
AU - Merlini, Giampaolo
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85108456629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85108456629&partnerID=8YFLogxK
U2 - 10.1038/s41375-021-01317-y
DO - 10.1038/s41375-021-01317-y
M3 - Article
C2 - 34168284
AN - SCOPUS:85108456629
SN - 0887-6924
VL - 36
SP - 225
EP - 235
JO - Leukemia
JF - Leukemia
IS - 1
ER -