Isatuximab, Carfilzomib and Dexamethasone (Isa-Kd) for the Management of Relapsed Multiple Myeloma

Abstract

The treatment of relapsed multiple myeloma remains challenging. Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial experience to date with Isa-Kd. Although final IKEMA results are pending, Isa-Kd has emerged as an effective and tolerable therapy for patients with relapsed multiple myeloma. Given the growing number of antibody-containing triplet regimens in this setting, potential niches and limitations for Isa-Kd are also discussed.

Lay abstract

For patients with multiple myeloma, navigating cancer relapses can be difficult. The combination of isatuximab, carfilzomib and dexamethasone (Isa-Kd), which was studied in the large ongoing IKEMA study, has recently been approved by government authorities in both the USA and Europe for treating multiple myeloma that has relapsed after initial therapy. Isatuximab is a drug that attacks the CD38 protein on myeloma cancer cells, while carfilzomib is a drug that prevents myeloma cancer cells from properly using and reusing proteins. Dexamethasone is a corticosteroid that has been shown to improve how well other antimyeloma drugs work. In this review, we discuss potential strengths and weaknesses of the Isa-Kd combination for patients with multiple myeloma that has relapsed.

Tweetable abstract

Isa-Kd (isatuximab, carfilzomib, dexamethasone): new option for relapsed myeloma based on Ph3 IKEMA trial. Review of evidence base and potential niche for Isa-Kd by @RahulBanerjeeMD @MilohemeRx @TomBmt133.

Keywords::

• carfilzomib
• isatuximab
• monoclonal antibodies
• multiple myeloma

Financial & competing interests disclosure

R Banerjee: Pack Health (research), Sanofi (consulting), SparkCures (consulting). M Lo: EUSA Pharma (consulting), Oncopeptides (consulting). T Martin: Amgen (research), GSK (consulting), Janssen (research), Juno (consulting), Roche (consulting), Sanofi (research), Seattle Genetics (research). 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.

No writing assistance was utilized in the production of this manuscript.

Company review disclosure

In addition to the peer-review process, with the authors’ consent, the manufacturer of the product discussed in this article was given the opportunity to review the manuscript for factual accuracy. Changes were made by the authors at their discretion and based on scientific or editorial merit only. The author maintained full control over the manuscript, including content, wording and conclusions.