Standard of Care in Newly Diagnosed Myeloma Remains as Carfilzomib Triplet Does Not Improve Outcomes

When compared to the current standard of care triplet of Velcade (bortezomib), Revlimid (lenalidomide) and Decadron (dexamethasone) (VRd), the combination of Kyprolis (carfilzomib), Revlimid and Decadron (KRd) does not improve progression-free survival (PFS) in newly diagnosed multiple myeloma, according to results of the ENDURANCE (E1A11) trial presented at the 2020 ASCO Virtual Scientific Program.

Because Kyprolis was found in recent phase 2 trials to be more effective, investigators sought to determine if the drug could replace Velcade in the current standard of care triplet in standard and intermediate risk newly diagnosed myeloma.

To do so, 1087 patients, with a median age of 65 years, were randomized 1:1 to either a Decadron-VRd or Decadron-KRd group for 36 weeks.

The trial also looked at whether indefinite maintenance with lenalidomide improves overall survival (OS) compared to 2-year maintenance. After being divided into VRd or KRd arms, a second 1:1 randomization was done, placing patients in either one group that would receive lenalidomide maintenance therapy for two years and another that would receive it indefinitely. For this phase, lenalidomide was given at 15mg on days one-21, every four weeks, and this portion of the study is still ongoing.

The VRd arm of 542 patients were given bortezomib at 1.3 mg/m² on days one, four, eight, and 11 (days one and eight for cycles nine through 12), lenalidomide at 25 mg on days one through 14, and dexamethasone at 40 mg on days one, two, four, five, eight, nine, 11, and 12 of a three-week cycle for 12 cycles.

The 545 patients in the KRd arm received carfilzomib at 36 mg/m² on days one, two, eight, nine, 15, and 16 with lenalidomide at 25 mg daily on days one through 21 and dexamethasone at 40 mg weekly, in four-week cycles for nine cycles.

In the VRd cohort, median PFS was 34.4 months compared to 34.6 months in the KRd arm.

In the VRd cohort, patients were taken off of the trial to pursue alternative therapies (18%), because of adverse events (17%), withdrawal (7%) or disease progression (6%).

The KRd arm saw patients removed due to pursuit of an alternative therapy (14%), adverse events (9%), disease progression and withdrawal (4% each).

The most common grade 3 or higher toxicities were non-hematological, appearing in 42% of patients in the VRd arm compared to 48% of patients in the KRd arm. While neuropathy rates were higher with VRd (8% compared to 1% in KRd), the KRd arm saw a significantly higher rate of cardio-pulmonary and renal toxicities (16% compared to 5% in the VRd arm).

Based on this analysis, researchers have concluded that VRd should remain the standard of care induction regimen in this population, and it should be the backbone for adding newer therapies for those patients.

Editor's Note: This article was updated on June 1, 2020, to correct information to make the information more accurate.