ASH 2024 | A Phase I/II trial of iberdomide for the treatment of intermediate- or high-risk smoldering myeloma

This is a Phase I/II trial looking at the role of iberdomide, which is a novel CELMoD, in the treatment of both intermediate and high-risk smoldering myeloma as defined by the 20-2-20 criteria. So this trial was really designed off of the ECOG E3A06 trial, or inspired by that design, which looks specifically at high-risk smoldering myeloma patients, randomized those patients to either lenalidomide alone until progression or observation. And what they saw in that trial was a three-year progression-free survival benefit, meaning a delay in the development of symptomatic myeloma of 91% in the treatment arm versus 66% in the observation arm. So really showing the benefit of lenalidomide and trying to delay or prevent the development of symptomatic myeloma. Because of the rate of discontinuation and the adverse event rate, the median time or average time on therapy was 23 months. So the authors concluded, let’s treat these patients with two years of lenalidomide, try to get that benefit without that added toxicity. 

So this trial used that design, essentially built upon it by using iberdomide, which is, as we know in the relapsed refractory myeloma space, more potent and better tolerated than lenalidomide and use it in the same way. So there was an initial safety run-in looking at both doses, 1.3 milligrams and 1.6 milligrams. There were no DLTs, but due to the rate of neutropenia, it felt to be safer to move forward with the 1.3 milligram dose. We’ve enrolled 22 patients to date, and we’ve presented that data at this meeting. 

And what we’ve found is two things that I think are really important. One is high overall response rate of 80% compared to about 50% what we saw in the ECOG study. And the second thing that I think is really promising is that it’s very well tolerated. So outside of neutropenia, which we are mitigating with dose reductions and trying to avoid G-CSF but using it when needed, outside of neutropenia, it’s very well tolerated. We’re seeing very minimal other AEs and they’re almost all grade one and two, outside again of hematologic AEs that have improved since we’ve decreased the dose. There are some recent trials looking at more novel therapies, T-cell engaging therapies and smoldering myeloma showing really high depth of response. But I think what we don’t know is if we really need that high depth of response in terms of time to progression or progression-free survival. So I think still a lot to learn and I think really promising. We’re very excited about the results to date.

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