Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis

Eli Muchtar, Morie A. Gertz, Betsy R. LaPlant, Francis K. Buadi, Nelson Leung, Patrick O'Brien, P. Leif Bergsagel, Amie Fonder, Yi Lisa Hwa, Miriam Hobbs, Dania K. Helgeson, Erin E. Bradt, Wilson Gonsalves, Martha Q. Lacy, Prashant Kapoor, Mustaqueem Siddiqui, Jeremy T. Larsen, Rahma Warsame, Suzanne R. Hayman, Ronald S. GoDavid Dingli, Taxiarchis V. Kourelis, Angela Dispenzieri, S. Vincent Rajkumar, Shaji K. Kumar

Research output: Contribution to journalArticlepeer-review


Bortezomib, a proteasome inhibitor (PI), has shown efficacy in the treatment of newly diagnosed and relapsed light chain (AL) amyloidosis, and is often used in combination with cyclophosphamide and dexamethasone. Ixazomib is the first oral PI to be approved in routine practice but has not yet been evaluated in the upfront treatment setting. Newly diagnosed AL amyloidosis patients with measurable disease and adequate organ function were enrolled. The primary objective was to determine the hematologic response rate of ixazomib in combination with cyclophosphamide and dexamethasone. Treatment was given for 12 cycles, followed by ixazomib maintenance until progression. Thirty-five patients were included; their median age was 67 years, and 69% were male. Major organ involvement included heart (66%) and kidneys (54%). A median of 4 induction cycles (range, 1-12) were administered. The overall hematologic response to induction was 63% and included complete response in 11.4% and very good partial response in 37.1% of patients. One patient was upstaged to complete response during maintenance. The most common reason for going off study was the institution of alternate therapy (61%). With a median follow-up of 29.7 months for the living patients, the 2-year progression-free survival and overall survival were 74% and 78%, respectively. The median time to alternate therapy was 7.5 months. Grade ≥3 hematologic and nonhematologic adverse events occurred in 23% and 49% of patients. Given ixazomib's favorable toxicity profile, which is an important advantage for the typically frail AL population, further evaluation of ixazomib in other combinations in the upfront setting is warranted.

Original languageEnglish (US)
Pages (from-to)5429-5435
Number of pages7
JournalBlood Advances
Issue number18
StatePublished - Sep 27 2022

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis'. Together they form a unique fingerprint.

Cite this