Project Description

Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Shaji Kumar, MD
Presented: May 31, 2020
Abstract ref: LBA3
Subtitles/Captions:

Authors: Shaji Kumar, Susanna J. Jacobus, Adam D. Cohen, Matthias Weiss, Natalie Scott Callander, Avina A. Singh, Terri L. Parker, Alex R. Menter, Xuezhong Yang, Benjamin Marshall Parsons, Pankaj Kumar, Prashant Kapoor, Aaron Seth Rosenberg, Jeffrey A. Zonder, Edward Anthony Faber, Sagar Lonial, Paul G. Richardson, Robert Z. Orlowski, Lynne I. Wagner, S. Vincent Rajkumar; Mayo Clinic, Rochester, MN; Dana-Farber Cancer Institute, Boston, MA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; ThedaCare, Appleton, WI; University of Wisconsin, Carbone Cancer Center, Madison, WI; MOHPA, Burnsville, MN; Yale University, Hamden, CT; Kaiser Permanente-Lone Tree, Lone Tree, CO; Saint Francis Cancer Center, Greenville, NC; Gundersen Health System, La Crosse, WI; Illinois CancerCare, Peoria, IL; University of California Davis Comprehensive Cancer Center, Sacramento, CA; Department of Malignant Hematology, Barbara Ann Karmanos Cancer Institute/Wayne State University School of Medicine, Detroit, MI; Oncology/Hematology Care, Inc, Cincinnati, OH; Winship Cancer Institute of Emory University, Atlanta, GA; Dana Farber Cancer Institute, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; Wake Forest University Health Sciences, Winston Salem, NC

Abstract Disclosures

Research Funding: U.S. National Institutes of Health

Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures).

Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy).

Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (<65 or ≥65), presence or absence of t(4;14) or ISS stage. The three-year OS (95% CI) was similar: VRd 84% (80 to 88) and KRd 86% (82 to 89).

Conclusions: In this randomized phase 3 trial, KRd did not improve PFS compared with VRd in NDMM. A significantly higher rate of cardio-pulmonary and renal toxicity was observed with KRd, while neuropathy rates were higher with VRd. VRd remains the standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550.

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Oral Abstract Presentation
Selected by the 2020 Annual Meeting Scientific Program Committee
Type: Oral Abstract Presentation
Presenter: Shaji Kumar, MD
Presented: May 31, 2020
Abstract ref: LBA3
Subtitles/Captions: