ASH 2025 | A real-world experience with TCE-pomalidomide salvage therapy in heavily pretreated multiple myeloma

So we identified 16 patients between January 24 and July 25 who had been treated with a median of six lines prior with multiple myeloma. We identified patients who had a combination of either talq or elra, which are both T-cell engagers, and pomalidomide, which is an immunomodulator. Our thinking was that when you’re on the sixth line or greater, really on the fourth line or greater, but an average between four to 10 was our population, you probably will have some element of T-cell exhaustion. And so the combination of a T-cell engager and an immunomodulator, which is designed to rescue some of that effector phenotype, like the CD8 positive or natural killer cells as well, might have a better response than either alone. And to select that population, we made sure that all 16 had had prior exposure to pomalidomide. So this was not their first exposure to pomalidomide. Most of them also had an anti-BCMA CAR-T as well, I believe 10 of 16, if memory serves. So they would have been exposed, most of them, to both conceptual lines of treatment. The T-cell engager was new. So eight of those 16, were treated with both from the start, and eight were treated with a T-cell engager therapy, and then POM was added, average of 1.1 months in, between, I think, 0.5 and three months. 

And I think 15 of 16 had partial response or better, 10 of 16 had very good partial response or better, and one had progression of disease. And that one was in the group that had the T-cell engager exposure, and then the POM was added afterwards. We found a favorable safety profile as well, essentially comparable. I think 77% had grade one CRS, which was mostly treated supportively, but occasionally did require standard of care, like steroids. 

So essentially, we were quite encouraged by this data. And we think that there’s data from newer generations, like iberdomide, of the same class of pomalidomide, where they do bone marrow phenotyping and they can see that actually there is a shift towards that effector cell phenotype, so maybe away from a more exhausted profile but certainly we can see towards an effector cell phenotype histologically. 

So I’ll talk about limitations limitations are there are, they’re two different groups. The addition of the pomalidomide therapies was on average 1.1 months. You can see deeper responses with T-cell engager therapies over time. So we’ll need further follow-up period. Our average follow-up was 5.5 months. So that’s one limitation. Another limitation is that we don’t have our bone marrow data ourselves. So we’re relying conceptually on the fact that in this iberdomide investigation, that seems to make sense. To demonstrate that, we would need to do those bone marrows in our own patients and prove that that’s what was in fact happening. But yeah, we were quite happy with the results, essentially confirmed our hypothesis, and we think we know why, but we can’t prove it without the bone marrows.

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