The triplet combination of ixazomib with lenalidomide and dexamethasone followed by maintenance with ixazomib may be a feasible treatment strategy for patients with newly diagnosed multiple myeloma (MM), according to results reported in Leukemia.
The phase 1/2 trial (ClinicalTrials.gov Identifier: NCT01217957) examined response and safety with ixazomib, lenalidomide, and dexamethasone as treatment for 65 patients with newly diagnosed MM.
Per cycle of induction therapy, patients were given ixazomib on days 1, 8, and 15 plus dexamethasone on days 1, 8, 15, and 22. Lenalidomide was given daily from days 1 through 21. Induction cycles were 28 days long and patients were treated for a maximum of 12 cycles.
A total of 23 patients discontinued induction to undergo stem cell transplantation (SCT). Among the 41 evaluable patients who remained on induction therapy, 80% experienced a response. A very good partial response (VGPR) or better was seen in 63% of patients, and 32% showed complete response.
Median progression-free survival (PFS) was 35.4 months for all patients and 29.4 months for those who completed induction instead of discontinuing for SCT.
Among the 25 patients who continued on ixazomib maintenance, 76% attained VGPR or better. Patients on ixazomib maintenance showed a median PFS of 37.2 months.
Adverse events during induction led to discontinuation of treatment in 9 of the 42 patients who did not undergo SCT. Adverse events that affected more than half of the total study population included diarrhea, fatigue, and nausea. Among all patients, neutropenia was the most common adverse event that reached grade 3 or more, affecting 22% of patients.
“In conclusion, the [triplet] combination offers a convenient all-oral regimen that combines the efficacy of a proteasome inhibitor and an immunomodulatory drug-based regimen for the treatment of newly diagnosed MM with a well-tolerated and manageable toxicity profile,” the authors concluded.
- Kumar SK, Berdeja JG, Niesvizky R, et al. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance [published online January 29, 2019]. Leukemia. doi:10.1038/s41375-019-0384