Velcade-Based Triplet Regimen ‘Should Remain’ Standard of Care in Newly Diagnosed Multiple Myeloma

A triplet regimen of Kyprolis (carfilzomib), Revlimid and dexamethasone (KRd) was not superior to the standard of care Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone(VRd) in patients with newly diagnosed standard- or intermediate-risk multiple myeloma, according to data published in The Lancet Oncology.

The data, according to the study authors, indicate that the VRd regimen should remain the standard of care for patients with newly diagnosed multiple myeloma.

In a multi-center phase 3 trial called ENDURANCE, researchers looked at 1,087 patients, 18 years or older, with newly diagnosed multiple myeloma and randomly assigned them to receive either the VRd regimen (approximately 542 patients) or KRd (approximately 545 patients). At a follow-up of 9 months, researchers found the median progression-free survival (PFS), the length of time during and after treatment the cancer does not progress in the patient, to be 34.6 months in the KRd group and 34.4 months in the VRd group. This was not a significant improvement to PFS, moreover, the KRd arm experienced more side effects and toxicity than the standard of care VRd.

“Grade 3-5 non-hematological (side effects) were reported more often in the KRd group than in the VRd group,” the authors wrote. “The KRd regimen was associated with a higher prevalence of cardiopulmonary and renal treatment-related (side effects) than was the VRd regimen, and there were more on-study deaths in the KRd group than in the VRd group.”

The most common serious or severe non-hematological side effects included fatigue in 6% of patients in both the VRd and KRd arms respectively, high blood sugar (4% vs 6%), diarrhea (5% vs 3%), peripheral neuropathy (8% vs less than 1%), shortness of breath (2% vs 7%) and thromboembolic events (2% vs 5%). Two treatment-related deaths occurred in the VRd group, one due to cardiotoxicity and another due to secondary cancer, while 11 treatment-related deaths occurred in the KRd group.

“Another important reason for the lack of difference in progression-free survival is the increased deaths seen in the KRd group,” the researchers wrote. “The higher rate of discontinuation with VRd for alternative therapy than with KRd is unlikely to have affected the results.”

VRd, the authors note, is a standard of care triplet regimen that has shown long-term efficacy and safety results in phase 2 trials for patients with newly diagnosed multiple myeloma. Adding the chemotherapy Velcade to the chemotherapy Revlimid and steroid dexamethasone significantly improved PFS and overall survival when compared to a combination of Revlimid and dexamethasone. However, in this trial neither VRd nor KRd reached their overall survival endpoints. In comparison, Kyprolis is a proteasome inhibitor that prevents proteasomes, cellular complexes that break down proteins like a garbage system does waste, from breaking down excess proteins. This buildup of proteins then helps to kill myeloma cells. Kyprolis is approved for the treatment of patients with relapsed multiple myeloma.

“Given its efficacy, safety, and convenience (i.e., subcutaneous vs intravenous infusion), the VRd regimen should remain the standard of care for patients with newly diagnosed multiple myeloma who are being considered for treatment with a triplet regimen,” the authors concluded.