How Does the Safety and Tolerability With Iberdomide Compare to Current IMiD Therapies?

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Dr. Patel:
Hello, my name is Krina Patel. I'm from UT MD Anderson Cancer Center. This presentation is on how does the safety and tolerability with Iberdomide compare to current emit therapy? So you will see two different papers referring to Lenalidomide and Pomalidomide treatment emersion AEs. So on the left is a review written by Palumbo et al in blood reviews from 2009 that basically looks at the treatment emergent AEs from Lenalidomide plus Dexamethasone and relapse refractory multiple myeloma. So here the authors concluded that compared to Talidomide, Lenalidomide does have markedly decreased rates of neuropathy, sedation, and constipation which for the time were all much appreciated.

However in clinical trials, the biggest grade three, four adverse events that they saw for Lenalidomide plus Dex in patients with multiple myeloma happen to be cytopenias, fatigue, muscle cramps, rash, infections, insomnia, and venous thromboembolism. And then on the right side we see a table that's from a Lancet Oncology paper in 2013 by San Miguel et al looking at the phase three study of Pomalidomide plus low dose Dex, which was a randomized study. So here you can see that grade three, four infections were about 30% anemia, about 33%, 34% neutropenia was 48% and fatigue at 5% thrombocytopenia about 22 to 23%. And you know, then it's a little bit less as the other symptoms, we go down the chart, but on the next slide we'll discuss CC-220 here, the rate response rates and safety, and this is Iberdomide, and again we're just going to focus on the safety portion which is on the right side of this slide. So here when you look at grade three, four side effects, really we are a little bit surprised that they're either similar or possibly even lower compared to some of the historical data from Len and Palm. Of course these have not been looked at side by side but just a great sort of reference to have for the 75 patients that got Iber plus Dex grade three, four anemia was about 26 - 27%, neutropenia was 33% with febrile neutropenia being about 5% of patients. Then thrombocytopenia was about 10%, infection about 21 - 22%. Fatigue was one patient, so 1.3%. We don't see any muscle spasms or diarrhea. That was 0% of patients for grade three, four. There's one patient with peripheral sensory neuropathy, so about 1.3%.

No deep vein thrombosis that were grade three, four and pulmonary embolism was about 1.3%. So again, just a very acceptable toxicity profile for relapse refractory patients. Here are the combinations that have been tested so far. And as we know, even with their usually depending on what you're combining with, you'll see a different toxicity profile. So this is looking at cohorts E, F and G in one of the big combination studies that's been done for Iberdimide for relapse refractory multiply patients. So the first cohort is Iber plus Daratumumab and Dex. The second cohort right there is Iber plus Vortezimide and Dex. And the third one is Iber plus Carfilzomidez. And what you see the neutropenia rates are still relatively similar or lower than expected I think for IberVd or IberKd. However, when Iber is with DARA we see that that neutropenia rate is 66.7% which is something we see similarly with our IMIDs plus the DARA combination. Again, the rates of thrombocytopenia and anemia are pretty similar across the different regimens and for nonhematological really they're very low grade three, four risks, infections being the biggest. And again, it seems that all of them have similar rates of infection, about 15 to 30%. So again, pretty tolerable in terms of toxicity for combinations in relapse refractory patients.

So take home points, CELLMods are safe and may have a favorable profile compared to IMIDs for certain toxicities such as neutropenia, but again, we need more studies. A combination with other therapies does increase some of the grade three, four toxicity, but remains manageable. And then hematological AEs and infections were the most common and were overall treatable. Thank you for your attention.

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