The efficacy of ixazomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone plus placebo was shown in the phase 3 TOURMALINE-MM2 trial for patients with newly diagnosed multiple myeloma who were not eligible for autologous stem cell transplant, according to a press release from Takeda.
The efficacy of ixazomib (Ninlaro) with lenalidomide (Revlimid) and dexamethasone versus lenalidomide and dexamethasone plus placebo was shown in the phase 3 TOURMALINE-MM2 trial (NCT01850524) for patients with newly diagnosed multiple myeloma who were not eligible for autologous stem cell transplant, according to a press release from Takeda.
The data, which was also presented at the 2020 Society of Hematologic Oncology (SOHO) Virtual Scientific Meeting, showed the ixazomib combination a median progression-free survival (PFS) increase of 13.5 months compared to the placebo combination, although the primary end point of PFS was not met and the trial did not meet the threshold for statistical significance. Ixazomib’s median PFS was 35.3 months versus 21.8 months with placebo (HR, 0.83; P =.073) after a median follow up of 57.8 months and 58.6 months, respectively.
Even though ixazomib plus lenalidomide and dexamethasone is approved for patients with multiple myeloma who received at least one prior therapy in over 65 countries, it has not been approved for this patient population.
“There is a specific need in newly diagnosed multiple myeloma, given there are currently no approved all-oral, proteasome inhibitor-based treatment options,” Thierry Facon, MD, of Lille University Hospital, who was the principal investigator and lead author of this study, said in a statement. “Findings from the TOURMALINE-MM2 trial are important overall for this patient population as well as across multiple subgroups including patients with high-risk cytogenetics. We hope these data will help inform future research and further progress for the multiple myeloma community.”
In this international, randomized, double-blind, multicenter, placebo-controlled study, patients with high-risk cytogenetics had a median PFS of 23.8 months with ixazomib compared with 18.0 months with placebo (HR, 0.69). There was also a complete response rate of 26% versus 14% in the ixazomib arm and placebo arm, respectively. The median overall survival was not reached in either arm at the time of follow-up (HR, 0.998), but the median time to progression was longer with ixazomib at 45.8 months than the placebo arm at 26.8 months (HR, 0.738).
For the toxicity profile, patients were observed to have diarrhea, rash, peripheral edema, constipation, and nausea as the most common treatment-emergent adverse events (TEAEs). There were TEAEs in 96.6% of patients and 92.6% of patients on the ixazomib combination and placebo combination, respectively, and 88.1% and 81.4% experienced grade 3 or more TEAEs. Thirty-five percent of patients discontinued on the ixazomib arm and 26.9% discontinued on the placebo arm. The was a rate of on-study deaths of 7.6% for ixazomib versus 6.3% for placebo.
“Insights from studies like TOURMALINE-MM2 are important, especially to those patients who may benefit from the convenience of treatment options that can be taken at home,” Paul Giusti, president and CEO of the Multiple Myeloma Research Foundation, said in a press release. “These critical learnings enable the community to comprehensively assess the different treatment combinations available for patients and physicians.”
This trial looked at 705 adult patients with newly diagnosed multiple myeloma who were ineligible for transplant for a primary end point of PFS and secondary end points including rate of complete response, pain response, and overall survival. Patients received ixazomib at 4 mg on days 1, 8, and 15; 25 mg of lenalidomide orally on days 1 through 21; and 40 mg of dexamethasone orally on days 1, 8, 15, and 22 every 28 days for the first 18 cycles. After cycle 18, ixazomib and lenalidomide were reduced and dexamethasone was discontinued. The placebo arm received the same amount of treatment with lenalidomide and dexamethasone.
“We hope the findings from the TOURMALINE-MM2 trial will encourage constructive conversations and help progress future research efforts, particularly for patients who could benefit from an all-oral, proteasome inhibitor-based combination that helps preserve quality of life,” Christopher Arendt, head of the Oncology Therapeutic Area Unit at Takeda, said in a statement. “As a company, we remain committed to the multiple myeloma community and look forward to sharing mature data from our ongoing phase 3 multiple myeloma maintenance studies in the future.”
Takeda announces results from phase 3 clinical trial evaluating Ninlaro (ixazomib) in newly diagnosed multiple myeloma. News release. Takeda. September 9, 2020. Accessed September 10, 2020. https://bit.ly/32fmF2F