Triplet Therapy With Ixazomib Shows Promise for Multiple Myeloma

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Notably, peripheral neuropathy — a common AE with proteasome inhibitors — had a low occurrence rate.
Notably, peripheral neuropathy — a common AE with proteasome inhibitors — had a low occurrence rate.

Triplet therapy with ixazomib, pomalidomide, and dexamethasone is effective, with a manageable safety profile, in patients with relapsed/refractory multiple myeloma (RRMM), according to a study published in Leukemia.1

For this open-label phase 1/2 study (ClinicalTrials.gov Identifier: NCT02119468), investigators administered oral pomalidomide, dexamethasone, and ixazomib to 32 patients with RRMM refractory to lenalidomide.

During the dose-exploratory phase 1 portion, patients received pomalidomide 4 mg, dexamethasone 40 mg, and ixazomib 3 mg (dose level [DL] 1) or 4 mg (DL2); the study continued with a standard 3 + 3 design, and decisions to escalate doses were based on dose-limiting toxicities (DLT).

At DL1, 1 of 3 patients experienced dose-limiting grade 3 fatigue and lung infection, and grade 4 neutropenia and thrombocytopenia; an additional 3 patients were enrolled and no further DLTs were observed. After escalating to DL2, 1 of 3 patients experienced dose-limiting grade 4 neutropenia, febrile neutropenia, and thrombocytopenia; 3 more patients were enrolled and had no further DLTs, establishing ixazomib's recommended phase 2 dose (RP2D) at 4 mg.

During phase 2, 19 additional patients were included and treated with the ixazomib RP2D, pomalidomide, and dexamethasone. After a median follow-up of 11.9 months, 48% of patients had at least a partial response and 20% of patients had a very good partial response; 76% reached at least stable disease.

The most frequently reported grade 2 or worse adverse events (AEs) included thrombocytopenia, anemia, neutropenia, and infections. Notably, peripheral neuropathy — a common AE with proteasome inhibitors — had a low occurrence rate.

The investigators concluded that “the findings justify further study of this combination for relapsed patients with myeloma who are refractory to lenalidomide, preferably with randomized comparisons to specifically identify clinical benefit.”

Reference

  1. Krishnan A, Kapoor P, Palmer JM, et al. Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma. Leukemia. 2018 Feb 23. doi: 10.1038/s41375-018-0038-8 [Epub ahead of print]

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