San Francisco, CA—Data from a phase 1/2 clinical trial support further evaluation of the investigational oral proteasome inhibitor ixazomib in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma. Approval of this drug would introduce an all-oral treatment regimen for this disease.
In a study reported at ASH 2014 by Shaji K. Kumar, MD, of the Mayo Clinic, Rochester, MN, long-term maintenance with ixazomib improved the depth of response after induction in patients with treatment-naïve myeloma. The overall response rate was 90%; complete response (CR) rate was 22% in patients after induction, which increased to 52% by the end of maintenance.
Of the 65 patients enrolled, 25 entered the maintenance phase and received a median of 31 total cycles (induction and maintenance) and 19 maintenance cycles.
“With maintenance, we saw a deepening of response in 48% of patients,” Dr Kumar reported. The rate of CRs plus near-CRs increased from 24% after induction to 62%, with 71% being very good partial responses or better. Ixazomib maintenance contributed to the durable responses, he said.
Half of the patients were still receiving maintenance therapy at the time of the report. The estimated percentage of patients surviving without progression at 2 years was 57%. Serious adverse events were observed in 4 (19%) patients during maintenance with ixazomib, none of which were considered to be related to treatment.
Ixazomib is the first oral proteasome inhibitor and has physiochemical properties distinct from bortezomib. The triplet of bortezomib, lenalidomide, and dexamethasone has been shown to produce high response rates, and increasing evidence suggests that extended treatment may add benefit to conventional induction strategies.
“Agents for continuous therapy, however, need to be convenient and well-tolerated,” Dr Kumar suggested. “Oral weekly ixazomib may be an ideal maintenance drug in terms of tolerability, safety, and convenience.”
“Single-agent ixazomib maintenance for up to 1.9 years was feasible, with a generally manageable safety profile, in patients not undergoing autologous stem-cell transplant,” he said. “New-onset toxicity during single-agent ixazomib maintenance was limited.”
Phase 3 trials that include patients who are newly diagnosed with myeloma and patients with relapsed myeloma are under way.