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Ixazomib combination confers durable responses in newly diagnosed myeloma
A combination regimen of ixazomib plus lenalidomide and dexamethasone conferred deep and durable responses among patients with newly diagnosed multiple myeloma, according to clinical study results presented at the Congress of European Hematology Association.
“Data showed that patients had deep responses on single-agent therapy and median PFS of more than 2 years,” Shaji K. Kumar, MD, professor of medicine at Mayo Clinic in Rochester, Minnesota, said in a press release. “We remain committed to gathering additional data of ixazomib in this investigational, maintenance setting.”
Researchers evaluated an all-oral combination of ixazomib (Ninlaro, Millennium Pharmaceuticals) — a proteasome inhibitor — plus lenalidomide (Revlimid, Celgene) and dexamethasone as an induction regimen among patients with newly diagnosed multiple myeloma.
In the current analysis, Kumar and colleagues evaluated long-term safety and efficacy data from patients who did not discontinue treatment in the trial to receive stem cell transplantation.
“Based on an increasing body of evidence that long-term therapy may improve clinical outcomes, this [phase 1/phase 2] trial focused on continuous treatment of patients with newly diagnosed multiple myeloma,” Kumar said in the press release.
The researchers assigned 65 patients weekly 1.68-3.95 mg/m2 ixazomib (days 1, 8, 15) plus 25 mg lenalidomide (days 1-21) and 40 mg dexamethasone (days 1, 8, 15, 22) for up to twelve 28-day induction cycles. Patients continued on weekly maintenance ixazomib as a single agent at the last tolerated dose until disease progression or toxicity.
The long-term analysis included 42 patients (median age, 68 years; range 34-86; 43% stage II disease) who continued treatment without early withdrawal for stem cell transplantation.
Median follow-up was 56 months.
As of October 18, 2016, patients achieved an overall response rate of 80% a complete with very good partial response rate of 63%; and complete response rate of 32%. The median duration to first response was 0.95 months and median time to complete response was 5.6 months.
Patients achieved a median PFS of 25.3 months. The median OS had not been reached at a median follow-up of 56 months; however, the researchers estimated 3-year OS of 87%.
Nearly three-quarters of patients (74%) experienced grade 3 or worse treatment-related adverse events and 26% of patients had treatment-related serious events. The most common treatment-related grade 3 or higher adverse events observed during the induction period included neutropenia (17%), thrombocytopenia (17%) and fatigue (14%). However, grade 3 or worse rash (7%) and peripheral neuropathy (5%) appeared uncommon.
One treatment-related death occurred due to respiratory syncytial viral pneumonia.
After completing all cycles of induction therapy, 25 patients received maintenance therapy. These patients achieved a 100% ORR — including a very good partial response rate of 44% and complete response rate of 32% — at the end of the induction period.
At data cutoff, ORR remained at 100%, with the very good partial response rate at 32% and complete response rate increasing to 44%. Median PFS for patients who received maintenance therapy was 24 months.
Common adverse events appeared confined to the induction period. No patients experienced grade 3 or worse peripheral neuropathy or rash during maintenance. – by Melinda Stevens
Reference:
Kumar SK, et al. Abstract S408. Presented at: Congress of European Hematology Association; June 22-25, 2017; Madrid.
Disclosure: Kumar reports research funding to the Mayo Clinic for clinical trials from AbbVie, Celgene, Janssen, Merck, Sanofi and Takeda; and consultant roles with Kesios, Noxxon and Skyline. Please see the abstract for a list of all other researchers’ relevant financial disclosures.