Treatment of newly diagnosed multiple myeloma with carfilzomib, lenalidomide, and dexamethasone (KRd) lacks superiority over treatment with bortezomib, lenalidomide, and dexamethasone (VRd), according to results from an interim analysis of a phase 3 clinical trial published in The Lancet Oncology.

The open-label, multicenter, phase 3 ENDURANCE trial ( Identifier: NCT01863550), included patients with newly diagnosed multiple myeloma who were not candidates for immediate autologous stem cell transplantation (ASCT). Eligible patients had Eastern Cooperative Oncology Group performance scores of 0 to 2 and did not have high-risk disease.

Patients were randomly assigned to receive induction treatment with either VRd (542 patients) or KRd (545 patients). Following this, a second randomization involved lenalidomide maintenance either indefinitely or for 2 years. The primary endpoint of focus for this interim analysis was progression-free survival (PFS) during the induction phase.

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The estimated median study follow-up for the interim analysis was 9 months. In intent-to-treat analysis, the KRd group had a median PFS of 34.6 months (95% CI, 28.8-37.8), and for the VRd group it was 34.4 months (95% CI, 30.1-not estimable), giving a hazard ratio (HR) of 1.04 (95% CI, 0.83-1.31; P =.74). Median overall survival, evaluated at a median of 26 months for the whole population, had not been reached with either treatment.

Safety was evaluated in 527 patients treated with VRd and 526 patients treated with KRd, reflecting patients who had received 1 or more treatment doses. Grade 3 to 4 fatigue occurred in 6% of patients in each treatment group. Grade 3 to 4 peripheral neuropathy was found in 8% of the VRd group and in less than 1% of the KRd group. Grade 3 to 4 thromboembolic events occurred in 2% of the VRd group and 5% of the KRd group.

Serious adverse events of grades 3 to 5 were more common with KRd (44%) than with VRd (22%; P <.0001). Fatalities deemed to be treatment related occurred in fewer than 1% of patients receiving VRd and in 2% of patients receiving KRd.

“The results of our trial show that the KRd regimen is not superior to the VRd regimen for initial treatment of patients with newly diagnosed standard-risk or intermediate-risk multiple myeloma who are ineligible for ASCT or who did not intend to have immediate ASCT,” wrote the study investigators in their report. The trial is continuing to evaluate patients during the maintenance phase.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Kumar SK, Jacobus SJ, Cohen AD, et al. Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. Published online August 28, 2020. doi:10.1016/S1470-2045(20)30452-6