A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis

Vaishali Sanchorawala, Giovanni Palladini, Vishal Kukreti, Jeffrey A. Zonder, Adam D. Cohen, David C. Seldin, Angela Dispenzieri, Arnaud Jaccard, Stefan O. Schönland, Deborah Berg, Huyuan Yang, Neeraj Gupta, Ai Min Hui, Raymond L. Comenzo, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review


This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory immunoglobulin light chain (AL) amyloidosis. Ixazomib was administered to adult patients with relapsed/ refractory AL amyloidosis after 1 or more prior lines of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4.A313 dose-escalation phase was followed by 2 expansion cohorts (PI-naive and PI-exposed patients) at the maximum tolerated dose (MTD). Twenty-seven patients were enrolled: 11 during dose escalation (6 at 4.0mgand5 at 5.5mg)and 16 during doseexpansion (4.0 mg). Three patients experienced dose-limiting toxicities: 1 at 4.0 mg and 2 at 5.5 mg; the MTD was determined as 4.0 mg. Mostcommonadverse events (AEs) included nausea, skin and subcutaneous tissue disorders (SSTD), diarrhea, and fatigue; grade 3 or higher AEs included dyspnea, fatigue, and SSTD. Overall, the hematologic response rate was 52% in patients treated at the MTD (n 5 21). Organ responses were seen in 56% of patients (5 cardiac, 5 renal). Median hematologic progression-free survival was 14.8 months; 1-year progression-free and overall survival rates were 60% and 85%, respectively (median follow-up, 16.9 months). Weekly oral ixazomib appears to be active in patients with relapsed/refractory AL amyloidosis, with a generally manageable safety profile. The study wasregistered at clinicaltrials.gov as #NCT01318902. A phase 3 study is ongoing (#NCT01659658).

Original languageEnglish
Pages (from-to)597-605
Number of pages9
Issue number5
Publication statusPublished - Aug 3 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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