EBMT 2022 | Benefits of CELMoDs over IMiDs in multiple myeloma

What I think we’re really excited about when it comes to the new CELMoDs, which are iberdomide, formerly known as CC-220 or CC-92480, is that while they may be structurally somewhat similar to their cousins or predecessors the IMiDs, they are far more potent, able to overcome drug resistance from those previous agents. And more importantly, seem to have different adverse event profiles as well. So when we see the data on iberdomide, for instance, what we’ve demonstrated quite nicely is that not only is it easy to combine with other commonly used anti-myeloma agents, such as daratumumab, carfilzomib, and bortezomib, but it is able to overcome the resistance of lenalidomide and pomalidomide, and even has activity in the context of prior BCMA-directed therapy which again is becoming a rapid unmet medical need, patients progressing on BCMA-directed therapy.
The other point about iberdomide that really I think is different from its predecessors really has to do with adverse events. And what we see in terms of adverse events is that the grade 3, grade 4 non-heme toxicity is virtually non-existent, which really speaks to some of the differences in chemistry and biochemistry of the compound, allowing it to potentially be a better partner and potentially have great utility, both in newly diagnosed and potentially even in the maintenance setting, where it seems to be much better tolerated than lenalidomide.
When we look at 92480, what we see is a compound whose biggest adverse events have to do with myelosuppression. So, cytopenias, predominantly neutropenia is the most common adverse event. But different from even iberdomide or other drugs in this class, what we also see is that it seems to have tissue penetration different from some of the other IMiDs or CELMoDs, allowing it to have very good activity in the context of extramedullary myeloma. And in the Phase I experience, we saw great data with that. And we’re now seeing additional data when combined with drugs, such as bortezomib that the extramedullary patient subset seems to do better with 480 than with any of the other drugs in this class. So, very exciting data on a number of different fronts.