KRd Fails to Improve Outcomes Compared With VRd in Newly Diagnosed MM

The next-generation proteosome inhibitor, carfilzomib plus lenalidomide and dexamethasone (KRd), failed to improve outcomes among patients with newly diagnosed multiple myeloma (MM) compared with standard-of-care bortezomib plus lenalidomide and dexamethasone (VRd), according to results of a phase 3 trial presented during the plenary session of the ASCO20 Virtual Scientific Meeting.

“VRd remains the standard triplet induction regimen in standard- and intermediate-risk NDMM, and a suitable backbone for 4-drug combinations,” Shaji K. Kumar, MD, of the Mayo Clinic in Rochester, MN, and lead author and presenter of the study, said.

Results from phase 2 trials suggested that KRd may have improved efficacy compared with VRd in newly diagnosed MM, which was the impetus for this phase 3 trial.

The ENDURANCE (E1A11) trial randomly assigned 1087 patients with newly diagnosed MM with no high-risk features to receive KRd or VRd for 36 weeks. After completion of therapy, a second randomization was performed to indefinite or 2 years of lenalidomide maintenance — these results are not yet mature at the time of the study presentation.

The primary endpoint for the first randomization was progression-free survival (PFS) and secondary endpoints included overall response rate (ORR), minimal residual disease (MRD) negativity, time to progression, overall survival (OS), and toxicity.

At baseline, the median patient age was 65 years and disease characteristics were well balanced between arms. There were 12.2% of patients who were black, which is important because this population is at a higher risk of aggressive disease, Dr Kumar said. There were more black patients enrolled in the phase 3 trial than what is typically observed in similar trials, he added.

There was no significant difference in overall survival (OS) or progression-free survival (PFS) in either arm. The median PFS was 34.6 months with KRd compared with 34.4 months with VRd (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P =.742).

The 3-year OS was 86% and 84% with KRd or VRd, respectively (HR, 0.98; 95% CI, 0.71-1.36; P =.923).

ORR was also similar between groups, with similar rates of complete response and stringent complete response. However, more patients in the KRd arm achieved very good partial response at 55.5% compared with 49.9% in the VRd arm (P =.002).

Adverse events (AEs) leading to discontinuation of the study occurred in 17.3% of cases in the VRd arm compared with 9.9% in the KRd arm. Grade 3 or higher TRAEs occurred in 47.8% and 52.3% of patients who received VRd or KRd, respectively. Peripheral neuropathy and cardiotoxicities were more common in the KRd group.

“In patients with newly diagnosed standard- or intermediate-risk myeloma not intended for early autologous stem cell transplant, KRd does not improve PFS compared with VRd,” Dr Kumar said.

Disclosure: The research described in this presentation was supported by Amgen. For a full list of disclosures, please refer to the abstract.

Reference

Kumar S, Jacobus SJ, Cohen AD, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr LBA3.  

This article originally appeared on Cancer Therapy Advisor