Ixazomib, dexamethasone, and rituximab (IDR) may be a safe and effective combination for patients with Waldenstrom macroglobulinemia (WM), according to a study published in Clinical Cancer Research.1

Proteasome inhibitors (PIs) administered as frontline therapy for WM are effective, but are associated with high rates of adverse events. There is a need for newer, more effective treatments with improved tolerability.

For this prospective phase 2 study (ClinicalTrials.gov Identifier: NCT02400437), researchers enrolled 26 patients with previously untreated WM and assigned them to receive oral ixazomib 4 mg, intravenous (IV) dexamethasone 20 mg, and IV rituximab 375 mg/m2. IDR was administered for 6 4-week cycles for induction therapy; patients who had a minor response or any clinical benefit continued on to 6 8-week maintenance cycles. All participants had an MYD88 L265P mutation, and 58% (15) of patients had a CXCR4 mutation.

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The median time to response (TTR) was 8 weeks. Patients with a CXCR4 mutation had a longer median TTR at 12 weeks compared with 8 weeks among patients with wild-type CXCR4 (P = .03). 

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The overall response rate (minor response [MR] or better) and major response rate (partial response [PR] or better) were 96% and 77%, respectively. The very good PR rate was 15%, the PR rate was 62%, and the MR rate was 19%.

The median progression-free survival was not reached after a median follow-up of 22 months.

The most frequently observed grade 2 or worse adverse events included insomnia, rash, and infusion-related reactions.

The authors concluded that “considering the response rate and excellent toxicity profile of IDR, we believe IDR represents another treatment option for the primary therapy of patients with WM.”


  1. Castillo JJ, Meid K, Gustine JN, et al. Prospective clinical trial of ixazomib, dexamethasone and rituximab as primary therapy in Waldenstrom macroglobulinemia. Clin Cancer Res. 2018 Apr 16. doi: 10.1158/1078-0432.CCR-18-0152 [Epub ahead of print]