The combination of the ixazomib, dexamethasone, and rituximab (IDR) yields durable responses and maintains an excellent safety profile in patients with Waldenström macroglobulinemia (WM), according to results of a study published in Blood Advances.

The investigators elected to assess IDR due to the favorable safety profile of ixazomib, in particular a low incidence of neuropathy, in multiple myeloma.

The long-term follow-up results included all 26 treatment-naive patients with WM who participated in the prospective, phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT02400437) that evaluated the combination of IDR.

For the study, IDR was administered over 12 cycles: six 4-week induction cycles followed by six 8-week maintenance cycles.


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All patients had the MYD88 L265P mutation, and CXCR4 mutations were present in 15 patients (58%). The median age at treatment initiation was 65 years (range, 46-82 years).

The median time to response was 2 months, and the median time to major response was 6 months. CXCR4 mutation status appeared to have an effect on the time to response; patients with CXCR4 mutations had a longer median time to response than those without mutations (3 months vs 1 month, respectively; P =.003). However, no significant difference was observed in the median time to major response between the genotypes (10 months vs 3 months, respectively; P =.31).

IDR induced high rates of response among the cohort. The overall response rate was 96% (95% CI, 80-100) while the major response rate was 77% (95% CI, 56-91). At best response, 19% of patients achieved a very good partial response (VGPR), 58% achieved a partial response, 19% had a minor response, and 4% had stable disease. The rate of VGPR was higher in patients without CXCR4 mutations than in patients with CXCR4 mutations (36% vs 7%; P =.06).

Among all patients, the median progression-free survival and median duration of response (DOR) was 40 months and 38 months, respectively. The median time to next treatment was also 40 months. None of these outcomes were associated with CXCR4 mutational status.  

The safety profile was considered excellent, although some patients experienced grade 3 adverse events, which included infections (2 patients, unrelated to treatment), hyperglycemia (2 patients, from dexamethasone), infusion reactions (2 patients, with rituximab), and neuropathy (1 patients, due to uncontrolled diabetes). No grade 4 adverse events or deaths occurred.

The authors concluded, “On the basis of the findings of our study, IDR represents an easy-to-administer, safe, and effective treatment option for patients with WM, with high rates of durable responses and an excellent adverse event profile.”

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Castillo JJ, Meid K, Flynn CA, et al. Ixazomib, dexamethasone, and rituximab in treatment-naive patients with Waldenström macroglobulinemia: long-term follow-up. Blood Adv. 2020;4(16):3952-3959. doi:10.1182/bloodadvances.2020001963

This article originally appeared on Hematology Advisor