There were similar rates of grade 3 to 4 treatment-related adverse events (AEs) between the VRd vs KRd group: fatigue (6% vs 6%), hyperglycemia (4% vs 6%), diarrhea (5% vs 3%), and thromboembolic events (2% vs 5%), respectively. The VRd group did have more cases of peripheral neuropathy compared with KRd (8% vs <1%, respectively) while the KRd group had more treatment related deaths (2%) compared to the VRd group (<1%).

The most common reasons for treatment-related death in the KRd group included cardiotoxicity (4 patients), acute kidney failure (2 patients), and respiratory failure (2 patients). Treatment-related cardiac, pulmonary, and renal toxicity of grades 3 to 5 were found in 16% of KRd patients compared with 5% of the VRd group (P <.0001). This difference was driven mostly by dyspnea and heart failure in the KRd group. Grade 3 to 5 serious AEs were statistically significantly more common in the KRd group compared with the VRd group (44% vs 22%, P <.001), but conversely, there were higher discontinuation rates in the VRd group (17% vs 10%, respectively). When specifically evaluating peripheral neuropathy, patients in the VRd group had higher rates of peripheral sensory neuropathy (7%) compared with KRd (1%).

The authors concluded that the KRd regimen did not improve PFS compared with VRd and had more adverse events, including treatment-related deaths. Therefore, the VRd regimen should continue to be considered the standard of care in patients with newly diagnosed MM who are not actively being evaluated for an ASCT. The KRd regimen did provide some benefit with less peripheral neuropathy, however this was overshadowed by the increased rates of other AEs.

Limitations of the study included exclusion of certain patients with high-risk disease, open-lab design, lack of formal ASCT eligibility criteria (and consequently lack of investigation into KRd as an induction therapy), and relatively high study discontinuation rates. The open-label nature of the study is especially important when evaluating the discontinuation rates, as those patients receiving bortezomib had to pay out of pocket for the medication compared to those receiving carfilzomib, as this medication was provided by the trial.


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It is clear that there is still a need for improving clinical outcomes in patients newly diagnosed with MM. It will be interesting to see if there are any significant changes to the OS data as more data are collected regarding the maintenance phase of the ENDURANCE study. Future studies may also aim to compare VRd to regimens that include daratumumab, which is an anti-CD38 mAb.

Disclosure: Some of the authors of the ENDURANCE study disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original study.

References

  1. 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. 2020;21(10):1317-1330. doi:10.1016/S1470-2045(20)30452-6
  2. Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X
  3. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750
  4. Kyprolis® (carfilzomib) [package insert]. Thousand Oaks, CA: Onyx Pharmaceuticals, Inc; 2020.
  5. Velcade® (bortezomib) [package insert]. Cambridge, MA: Millenium Pharmaceuticals, Inc; 2019.