ENDURANCE: Comparing KRd With VRd in Newly Diagnosed Myeloma

Initial treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) was not associated with longer progression-free survival (PFS) compared with bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (MM), according to findings from the phase III ENDURANCE trial presented by Shaji Kumar, MD, of Mayo Clinic in Rochester, Minnesota. The study was a late-breaking abstract in the ASCO20 Virtual Scientific Program.

The ENDURANCE trial (NCT01863550) enrolled 1,087 patients with symptomatic newly diagnosed MM in the absence of del17p, t(14;16), and t(14;20), as evidenced by fluorescence in situ hybridization (FISH) testing on bone marrow, and without plasma cell leukemia or a high-risk GEP70 profile. Patients were randomly assigned 1:1 to:

  • VRd (n=542): bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 (days 1 and 8 for cycles 9-12), lenalidomide 25 mg on days 1 to 14, and dexamethasone 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 3-week cycle for a total of 12 cycles
  • KRd (n=545): carfilzomib 36 mg/m2 on days 1, 2, 8, 9, 15, and 16, lenalidomide 25 mg daily on days 1 to 21, and dexamethasone 40 mg weekly, in 4-week cycles for a total of 9 cycles

Treatment was administered for 36 weeks and was followed by a second random allocation to indefinite treatment versus 2 years of maintenance with lenalidomide 15 mg on days 1 to 21 every 4 weeks. The primary outcome measures included PFS for the induction analysis and overall survival (OS) for the maintenance analysis. The maintenance data are not mature and have not yet been reported.

At time of randomization, the median age of the overall cohort was 65 years. The median induction duration for the VRd and KRd groups were 5.9 and 8.2 months, respectively. Disease progression was observed in 6% of patients randomized to VRd and 4% of patients randomized to KRd, which was not a statistically significant difference.

A higher proportion of patients assigned to VRd experienced an adverse event (17% vs. 9%) and 7% of patients in the VRd arm withdrew from the study compared with 4% of patients assigned to KRd. Grade ≥3 non-hematologic toxicities were observed in 42% of VRd-treated patients and 48% of KRd-treated patients. A higher proportion of grade ≥3 composite cardiac, pulmonary, and renal events occurred in the KRd group (16% vs. 5%). In addition, 8% of patients in the VRd group experienced grade ≥3 peripheral neuropathy during treatment compared with 1% of patients in the KRd group.

Approximately 83% of patients in the VRd treatment group and 86% of patients in the KRd arm experienced a partial response or better. A very good partial response or better was observed in 43% of patients randomized to VRd and 49% of patients randomized to KRd. A complete response was experienced by 10% of patients in the VRd group and 14% of patients in the KRd arm.

The PFS was not significantly different between the groups at the second of three planned interim analyses (median PFS for VRd and KRd = 34.4 months vs. 34.6 months, respectively; p=0.74). There were also no differences between the groups in terms of PFS based on age (<65 vs. ≥65 years), presence or lack of t(4;14), or International Staging System stage. Additionally, there was a similar 3-year OS survival rate in the VRd (84%) and KRd (86%) treatment arms.

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. J Clin Oncol 38: 2020 (suppl; abstr LBA3). Presented as part of the ASCO20 Virtual Scientific Program. May 29-31, 2020.