Iberdomide in combination with dexamethasone for multiple myeloma

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Published: 25 Sep 2019
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Prof Sagar Lonial - Winship Cancer Institute, Atlanta, USA

Prof Sagar Lonial talks to ecancer at the International Myeloma Workshop 2019 about iberdomide.

Iberdomide is a novel cereblon E3 ligase modulator with enhanced tumoricidal and immunostimulatory activities.

It overcomes IMiD immunomodulatory drug resistance and has synergy with daratumumab, bortezomib, and dexamethasone.

Prof Lonial outlines some of the data from the trial focussing on the combination with dexamethosone, as well as toxicity profile.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

I presented today on iberdomide which is the fourth generation IMiD compound, a cousin of thalidomide, lenalidomide and pomalidomide. What iberdomide does that the others don’t do is bind cereblon even more potently than the other ones do and has different downstream effects on Ikaros and Aiolos, allowing it to work to overcome the resistance to pomalidomide and lenalidomide.

This was a phase I multi-arm trial that was iberdomide alone, there was iberdomide plus dexamethasone and now that there are expansion cohorts combining iberdomide with bortezomib, daratumumab and carfilzomib. What I’m focussing on in the presentation is really the use of iberdomide with dexamethasone where a total of 66 patients have gone through dose escalation at this time.

So what we were most excited about was about a 30% overall response rate even in the context of pomalidomide and, in many cases, daratumumab resistant myeloma. The adverse events were pretty well tolerated, there was only some hematologic toxicity. In general it looks like it’s tolerated better than many of the other IMiD class of drugs that we’ve used.

What are the next steps?

The next steps are to continue to work on the dose escalation with combinations and to try to find the maximum tolerated dose, or MTD. We haven’t hit that yet in the dexamethasone combination. Then, again, find the combination doses with carfilzomib, bortezomib, daratumumab and potentially other antibodies as a way to try to figure out how to use this as a tool going forward.

How do you think this could impact clinical practice?

This is really addressing an area where there is a huge unmet need in myeloma and that is patients with pomalidomide and potentially daratumumab and carfilzomib resistant myeloma. So the ability to get a one in three response rate in this patient population is very exciting and offers these patients new options.