Daratumumab subcutaneous formulation for the treatment of multiple myeloma

ABSTRACT

Introduction

Intravenous daratumumab has shown unprecedented anti-myeloma activity when used as a single agent or in combination with other myeloma therapies. Recently, a subcutaneous formulation of daratumumab was approved for use in both the United States and European Union based on data which showed shorter infusion times and decreased rate of infusion reactions while maintaining non-inferior efficacy.

Areas covered

We cover the physiology behind subcutaneous daratumumab and summarize the relevant clinical data with a particular focus on the pharmacokinetics, pharmacodynamics, safety, and clinical efficacy. Articles used to generate this review were obtained by searching pubmed (https://pubmed.ncbi.nlm.nih.gov/) with the search terms ‘subcutaneous daratumumab’ and ‘daratumumab hyaluronidase’.

Expert opinion

Subcutaneous daratumumab is associated with lower risk of infusion reactions and decreased administration time while maintaining non-inferior efficacy. We support the use of subcutaneous daratumumab for all approved indications and for investigational use moving forward.

KEYWORDS:

• Daratumumab
• multiple myeloma
• subcutaneous

Article highlights

• Subcutaneous daratumumab was shown to be non-inferior to intravenous daratumumab in the phase 3 COLUMBA trial.

• Rates of infusion reactions have been significantly lower with subcutaneous daratumumab compared to intravenous daratumumab.

• Subcutaneous daratumumab is administered over a period of 3-5 minutes resulting in decreased time at infusion centers, less lost work hours, and improved quality of life.

• Flat dosing with 1800 mg subcutaneous daratumumab achieved therapeutic concentrations across a wide range of patient weights.

• Subcutaneous daratumumab was associated with a small increased risk of neutropenia, but overall was well tolerated.

• Preliminary data with subcutaneous daratumumab in combination with other myeloma backbones has yielded similar efficacy to analogous combinations with intravenous daratumumab.

This box summarizes key points contained in the article.

Declaration of interest

SZ Usmani declares research funding from Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda; consulting fees from Amgen, BMS, Celgene, GSK, Janssen, Merck, Sanofi, SkylineDx, Takeda and speaking fees from Amgen, Celgene, Janssen, Takeda. B Paul declares consulting fees from Regeneron and Amgen; speakers fees from Amgen and stock ownership in Bristol-Myers Squibb (prior employee). 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.