Philippe Moreau, MD
In November 2015, the FDA approved ixazomib (Ninlaro) in combination with lenalidomide (Revlimid) and dexamethasone as a treatment for patients with multiple myeloma who have received at least 1 prior therapy.
The approval was based on data from the phase III TOURMALINE-MM1 trial, which showed a median progression-free survival (PFS) of 20.6 months with ixazomib plus lenalidomide and dexamethasone compared with 14.7 months with lenalidomide and dexamethasone alone.
The overall response rate (ORR) with ixazomib was 78.3% compared with 71.5% for lenalidomide and dexamethasone alone (odds ratio [OR], 1.44; P
= .035) and the complete response rate with ixazomib was 11.7% versus 6.6% with the doublet (OR, 1.87; P
The study included 722 patients with a median age of 66 years. Fifty-nine percent of patients had received 1 prior therapy and 77% had relapsed multiple myeloma. Overall, 88% of patients were ISS stage I/II and 19% had high-risk cytogenetics by FISH criteria.
The study and the corresponding approval are extremely significant, says Philippe Moreau, MD, head of Department of Hematology, Centre Hospitalier et Universitaire in Nantes, France.
“This is a very, very important study,” says Moreau. “I think that it is a huge advancement for the field.”
In an interview with OncLive
, Moreau further discusses the significance of ixazomib and the TOURMALINE-MM1 study, as well as the benefit of an oral regimen for the treatment of patients with relapsed multiple myeloma.
OncLive: What were the goals of the TOURMALINE-MM1 trial?
: The TOURMALINE-MM1 study is a prospective, randomized, double-blind, placebo-controlled study comparing lenalidomide, dexamethasone, and placebo with lenalidomide, dexamethasone, and ixazomib. The combination of lenalidomide and dexamethasone is currently one of the standards of care in the relapse setting. Ixazomib was the first oral proteasome inhibitor available.
The goal of the study was to look at the PFS of patients receiving the combination of lenalidomide, dexamethasone, and ixazomib. The main inclusion criteria were relapsed and refractory myeloma with 1 to 3 prior lines of treatment.
What are the most significant results?
We showed that the duration of response and PFS are highly significantly improved with the addition of ixazomib. The benefit is a 6-month improvement in PFS. All subgroups of patients are benefiting from the addition of ixazomib to lenalidomide and dexamethasone, including the younger population of patients, patients older than 75, patients previously exposed to bortezomib (Velcade), and patients with eitherstandard or high-risk cytogenetics.
Through a special focus on cytogenetics, we were able to show that the PFS in the ixazomib group was basically identical to the PFS in patients with standard-risk cytogenetics. It means a lot.
From a safety point of view, the triplet is very safe. The addition of ixazomib is not adding any toxicity. We don’t have any rash issues as we did in the phase I early development of the drug. We have more thrombocytopenia, but it does not result in a higher frequency of bleeding; more transfusions are not required. Overall, the results are very important.
What impact does the option of an oral triple combination have on patients?
This is the first all-oral triple combination for the treatment of this disease. It is very effective, safe, and convenient. Patients are able to take the drug at home. The drug is administered orally at 4 mg on days 1, 8, and 15. Lenalidomide is administered orally at 25 mg on days 1 to 21, and dexamethasone is administered orally at 40 mg on days 1, 8, 15, and 22. It is very convenient.
Carfilzomib (Kyprolis), which is a very effective drug for this patient population, requires patients to return to the hospital 6 times a month to receive an IV infusion. With bortezomib, patients have to go to the hospital 4 times every 3 weeks. We are now moving to an all-oral regimen and that convenience is very, very important for the patient.
Do you think triplet regimens are going to become more common in the relapsed setting?
I think we are really moving from a 2-drug standard to a 3-drug standard in the relapsed setting.
We have several trials looking at lenalidomide, dexamethasone, and a third drug. We have data on lenalidomide and dexamethasone plus elotuzumab as well as lenalidomide and dexamethasone plus carfilzomib. Now, we have data on lenalidomide and dexamethasone plus ixazomib. Very soon, we will have data on lenalidomide and dexamethasone plus daratumumab (Darzalex).
Triple combinations will likely become widely used. The questions now are, “How are we going to use these different regimens? How are we going to select the optimal option?” That is something that is still unclear. Discussing with the patients what their preferences are will become very important.