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

Angela Dispenzieri, Efstathios Kastritis, Ashutosh D. Wechalekar, Stefan O. Schönland, Kihyun Kim, Vaishali Sanchorawala, Heather J. Landau, Fiona Kwok, Kenshi Suzuki, Raymond L. Comenzo, Deborah Berg, Guohui Liu, Arun Kumar, Douglas V. Faller, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis'. Together they form a unique fingerprint.

Cite this