Top Takeaways from ASH: Triple therapy with ixazomib is first fully oral regimen for multiple myeloma

Ixazomib, the first oral proteasome inhibitor to receive FDA approval, improved PFS for patients with relapsed, refractory multiple myeloma when used in combination with lenalidomide and dexamethasone without a substantial increase in toxicity.

“The interesting – and important – thing is that this [regimen] is a totally oral treatment,” said John Sweetenham, MD, chief medical editor of hematology for HemOnc Today and senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at University of Utah. “It’s the first oral 3-drug combination for multiple myeloma.”

John Sweetenham

The combination could become “a new standard of care in this setting,” according to findings presented at the ASH Annual Meeting and Exposition.

Tourmaline-MM1 Study

The phase 3 Tourmaline-MM1 study from Philippe Moreau, MD, head of hematology at University of Nantes in France, and colleagues enrolled adult patients with relapsed, refractory multiple myeloma who had one to three prior lines of therapy.

Patients were randomly assigned to a 28-day treatment cycle of lenalidomide (25 mg, days 1 through 21) and dexamethasone (40 mg, days 1, 8, 15 and 22) with 4-mg ixazomib (n = 360) or placebo (n = 362) on days 1, 8 and 15. Treatment cycles continued until disease progression or unacceptable toxicity.

The median number of cycles for ixazomib (Ninlaro, Takeda Pharmaceuticals), lenalidomide (Revlimid, Celgene) and dexamethasone was 13 (1-26). Patients treated with lenalidomide, dexamethasone and placebo were treated with a median number of 12 (1-25) cycles.

Patients treated with ixazomib experienced significantly longer PFS than patients assigned to the placebo group (20.6 months vs. 14.7 months; HR = 0.74; 95% CI, 0.58-0.93). OS data was not mature at the time study results were presented.

Adverse events seen with the triple therapy combination were consistent with the safety profiles of each individual agent. The most common grade 3 or higher adverse events in the ixazomib and placebo arms included neutropenia (19% vs. 16%), anemia (9% vs. 13%), thrombocytopenia (13% vs. 5%) and pneumonia (6% vs. 8%). Study drug discontinuation due to adverse events occurred in 13% of patients receiving ixazomib vs. 11% receiving placebo; 5% of patients in the ixazomib arm died during treatment compared with 3% in the placebo arm.

Improved PFS, manageable toxicity

The PFS results among patients treated with ixazomib vs. placebo – 20.6 months vs. 14.7 months – is “a highly significant improvement,” Sweetenham said, and “a very interesting result.”

Mitchell R. Smith, MD, PhD, director of the Lymphoid Malignancy Program at Cleveland Clinic Taussig Cancer Institute, highlighted the benefits of this treatment approach in regard of adverse events.

Mitchell R. Smith

“For patients who have had a lot of treatment, it’s nice to have an oral regimen,” Smith said. “The side effects are pretty manageable. There’s not much neuropathy, which is the big problem with bortezomib (Velcade, Millennium Pharmaceuticals).”

These two factors – the oral delivery and manageable side effect profile – will make ixazomib, approved by the FDA in November, “a useful agent,” according to Smith. – by Julia Ernst, MS

Reference:

Moreau P, et al. Abstract 727. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: Moreau reports honoraria from and advisory roles with Bristol-Myers Squibb, Celgene, Janssen-Cilag, Millennium Pharmaceuticals and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.