A combination of carfilzomib, dexamethasone, and daratumumab for treatment of adult patients with relapsed/refractory multiple myeloma in two dosing regimens: once-weekly and twice-weekly

ABSTRACT

Introduction: Despite the development of new therapeutic agents, relapsed/refractory multiple myeloma (RRMM) is associated with poor survival outcomes. Furthermore, many patients develop resistance to immunomodulatory drugs (IMiD), creating a need for IMiD-free regimens. Areas covered: This review focuses on the combination of carfilzomib, dexamethasone, and daratumumab (KdD or DKd) which has shown promising results in patients with RRMM who have tried multiple lines of therapy, and has been approved in the U.S., EU, and Japan. The KdD triplet has two recommended dosage regimens, carfilzomib once-weekly (KdD70 QW) and carfilzomib twice-weekly (KdD56 BIW), with comparable efficacy and safety profiles. Expert opinion: These options provide flexibility to patients and healthcare providers, especially in the era of COVID-19. Carfilzomib-based regimens remain a standard of care based on multiple randomized phase 3 studies. Additional studies are currently underway investigating carfilzomib-based regimens such as KdD combined with novel agents. Nevertheless, KdD is one of the most efficacious options for patients with RRMM.

KEYWORDS:

• Carfilzomib
• daratumumab
• dexamethasone
• multiple myeloma
• proteasome inhibitor

Article highlights

• Patients with RRMM typically have poor survival outcomes and decreased responses with each new regimen

• KdD is approved in the U.S., EU, Japan, and Canada for patients with RRMM who have undergone 1–3 prior lines of therapy

• There are two recommended dosage regimens for KdD: KdD70 QW and KdD56 BIW

• Both regimens have been shown to be efficacious and safe in clinical trials; a cross-study comparison showed comparable efficacy and safety profiles for the two regimens

• The existence of two KdD dosage regimens offers flexibility to patients and healthcare providers, especially in the time of COVID-19

• Ongoing studies are focusing on new combination regimens (e.g., quadruplets), with carfilzomib-based regimens combined with new agents being one of the most promising paths forward

Acknowledgments

The authors thank G Johnson, PhD (ICON, North Wales, PA), whose work was funded by Amgen Inc., for medical writing assistance in the preparation of this manuscript.

Declaration of interest

X Leleu reports honoraria from AbbVie, Amgen Inc., CARsgen, Celgene, GlaxoSmithKline, Incyte, Janssen, Merck, Novartis, Sanofi, and Takeda. A Chari reports research funding from Amgen Inc., Celgene, Janssen, Millennium/Takeda, Novartis, Pharmacyclics, and Seattle Genetics; has served in an advisory role for Amgen Inc., Celgene, Janssen, Karyopharm, Novartis, Oncopeptides, Sanofi, and Seattle Genetics; and consulting fees from Amgen Inc., Bristol-Myers Squibb, Celgene, Janssen, Millennium/Takeda, and Novartis. S Richard has nothing to disclose. M Khurana is an employee and stockholder of Amgen. A Yusuf is an employee and stockholder of Amgen. S Z Usmani reports research funding from Amgen, Array Biopharma, Bristol-Myers Squibb, Celgene, Glaxo-SmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; consulting fees from Amgen, Bristol-Myers Squibb, Celgene, EdoPharma, GlaxoSmithKline, Janssen, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, and TeneoBio; and speaking fees from Amgen, Bristol-Myers Squibb, Janssen, and Sanofi.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.