KRd vs VRd as Induction Therapy for Myeloma

Dr. Carlyn Tan presents the results of a study on Carfilzomib, Lenalidomide and Dexamethasone (KRd) Vs Bortezomib, Lenalidomide, and Dexamethasone (VRd) as induction therapy in newly diagnosed High-Risk Multiple Myeloma (HR-NDMM).

Abstract title:

Carfilzomib, Lenalidomide and Dexamethasone (KRd) Vs Bortezomib, Lenalidomide, and Dexamethasone (VRd) As Induction Therapy in Newly Diagnosed High-Risk Multiple Myeloma

Purpose of the trial:

Bortezomib, lenalidomide, dexamethasone (VRd) and carfilzomib, lenalidomide, dexamethasone (KRd) are standard induction regimens for the treatment of newly diagnosed multiple myeloma (NDMM). The phase III ENDURANCE trial excluded patients with high-risk NDMM (HR-NDMM) and included patients with no intention for immediate autologous stem cell transplant (ASCT) (Kumar SK, et al. Lancet Oncol 2020). Herein, we examined outcomes associated with KRd and VRd induction in the management of HR-NDMM.

Video summary:

We conducted a multivariate analysis for important clinical variables that may affect survival outcomes. Multivariable analysis for PFS showed that KRd induction (HR=1.80; 95%CI, 1.05-3.10; P=0.033) and R-ISS Stage I compared to R-ISS Stage II (HR=2.67; 95%CI, 1.33-5.38; P=0.006) and R-ISS Stage III (HR=3.51; 95%CI, 1.02-12.07; P=0.046) were associated with better PFS. Early ASCT was not associated with improvement of PFS on multivariable analysis (P=0.30). Age, cardiac history, and achieving CR/sCR or VGPR/PR compared to <PR as the best response to induction did not have a statistically significant effect on PFS.

Conclusions:

There was a significant improvement in PFS among HR-NDMM patients who received KRd compared to VRd induction. In patients who received early ASCT, we did not observe a statistically significant difference in PFS or OS between the two induction regimens, but this analysis is subject to inherent selection bias. Until results from prospective randomized studies are available for HR-NDMM patients, the use of various induction regimens in transplant-eligible patients opting for early transplant should be tailored to each patient.

Trial information:

ASH 2022: Abstract #752

Authors:

Carlyn Tan, MD1, David Nemirovsky, MS2*, Andriy Derkach, PhD2*, Malin Hultcrantz, MD, PhD1, Hani Hassoun, MD1, Sham Mailankody, MBBS 3, Urvi A Shah, MD1, Dhwani Patel, MD1*, Kylee H Maclachlan, MBBCh, PhD1, Oscar B Lahoud, MD3, Gunjan L. Shah, MD3*, Michael Scordo, MD3, David J. Chung, MD, PhD3, Heather Landau, MD3, Sergio A Giralt, MD3, Alexander M Lesokhin, MD1, Neha Korde, MD1 and Saad Usmani, MD4,5