Patients non-eligible for transplant

ELOQUENT-1 and TOURMALINE-MM2 studies report no improvement in PFS in patients with newly diagnosed MM

This week, data from two phase III clinical trials, ELOQUENT-1 and TOURMALINE-MM2, conducted in patients with transplant ineligible newly diagnosed multiple myeloma (NDMM), were announced. Both studies did not meet their primary endpoints, of a significant improvement in progression-free survival (PFS) with the addition of elotuzumab (E) or ixazomib (I) to the standard lenalidomide and dexamethasone (Rd) combination, respectively.1,2

ELOQUENT-11

ELOQUENT-1 (NCT01335399) is a randomized, open-label, phase III study evaluating the combination ERd, vs Rd in transplant-ineligible patients with NDMM. The primary endpoint is PFS, and secondary endpoints include objective response rate and overall survival (OS).

The analysis revealed that there was no statistical improvement in PFS with ERd compared with Rd. The safety profile of ERd was consistent with that previously reported for the same combination in the relapsed and refractory setting in the  ELOQUENT-2 trial. The results of a full ELOQUENT-1 data evaluation will be presented at a future medical meeting.

The  ERd combination has been previously approved by the US Food and Drug Administration (FDA) and European Medicines Agency for the treatment of adult patients with MM, who received one to three prior therapies.3,4 Elotuzumab in combination with pomalidomide and dexamethasone is also approved by the FDA and the EMA for the treatment of adult patients after ≥ 2 prior therapies including lenalidomide and a proteasome inhibitor.3,4 (Read about the approval by the FDA here and the European Commission here.)

TOURMALINE-MM22

TOURMALINE-MM2 (NCT01850524) is a randomized, double-blind, placebo-controlled phase III clinical trial evaluating IRd vs placebo plus Rd, in transplant-ineligible patients with NDMM (N = 705). The primary endpoint is PFS and secondary endpoints include complete response rate and OS.

The analysis demonstrated non-significant 13.5 months improvement in PFS in the IRd group vs Rd group (35.3 vs 21.8 months; HR 0.83; p = 0.073). The safety profile was generally consistent with previous reports.5

Despite the study not meeting the primary endpoint with statistical significance, a 13.5-month improvement in PFS indicates the oral IRd combination may still have a role in the treatment of NDMM, specifically for patients who are older with comorbidities, or those who cannot travel easily for treatment.

The IRd combination has been previously approved by the FDA and EMA for the treatment of patients with MM who have received ≥ 1 prior therapy.6,7 Ixazomib is also being investigated in other combinations and indications. (Read about IRd as a consolidation treatment, ixazomib in combination with thalidomide and dexamethasone for RR MM and ixazomib maintenance in NDMM).

References
  1. Bristol Myers Squibb. Bristol Myers Squibb Reports Primary Results of ELOQUENT-1 Study Evaluating Empliciti (elotuzumab) Plus Revlimid (lenalidomide) and Dexamethasone in Patients with Newly Diagnosed, Untreated Multiple Myeloma. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-reports-primary-results-eloquent-1-study- Published March 9, 20202 [Accessed March 11, 2020]
  2. Takeda. Takeda Provides Update on TOURMALINE-MM2 Phase 3 Trial. https://www.takeda.com/newsroom/newsreleases/2019/takeda-provides-update-on-tourmaline-mm2-phase-3-trial/ Published March 10, 2020 [Accessed March 11, 2020]
  3. European Medicines Agency. Empliciti. https://www.ema.europa.eu/en/medicines/human/EPAR/empliciti [Accessed 2020 Mar 11]
  4. U.S. Food & Drug Administration. Empliciti. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761035s008lbl.pdf [Accessed 2020 Mar 11]
  5. Ninlaro. Summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/ninlaro-epar-product-information_en.pdf [Accessed March 11, 2020]
  6. European Medicines Agency. Ninlaro. https://www.ema.europa.eu/en/medicines/human/EPAR/ninlaro [Accessed 2020 Mar 11]
  7. U.S. Food & Drug Admininistration. Ninlaro label, https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdf [Accessed 2020 Mar 11]
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