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Twice-Weekly Ixazomib May Benefit Some Patients With Newly Diagnosed Multiple Myeloma

By: Sarah Campen, PharmD
Posted: Tuesday, August 21, 2018

According to a recent study published in the British Journal of Haematology, twice-weekly ixazomib plus lenalidomide and dexamethasone appears to improve long-term outcomes in patients with newly diagnosed multiple myeloma. However, twice-weekly dosing of the triplet therapy may be associated with greater toxicity than weekly dosing, found Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues.

“Further investigation of twice-weekly dosing is potentially warranted to define a subset of patients who are able to tolerate, and benefit from, more intensive therapy,” stated the investigators.

In phase I of the study, 14 patients were given ixazomib twice weekly at escalating doses. The recommended phase II dose was determined to be 3 mg, based on overall tolerability over multiple cycles. An additional 50 patients participated in phase II, receiving ixazomib at 3 mg twice weekly plus lenalidomide and dexamethasone for up to 48 weeks, followed by maintenance with twice-weekly ixazomib alone.

The overall response rate was 94%, with a median progression-free survival of 24.9 months. Very good partial responses and complete responses were observed in 68% and 24% of patients who responded to therapy, respectively. Responses were “rapid, deep, and durable, deepening over the course of treatment,” according to Dr. Richardson and colleagues.

As for toxicity, grade 3 treatment-related adverse events were reported in 64% of patients, including rash (13%), peripheral neuropathy (8%), and hyperglycemia (8%). Although adverse events appeared to be similar to those reported with once-weekly therapy in a separate study, more patients receiving twice-weekly treatment required dose reduction than did those receiving once-weekly treatment (66% vs. 20%).