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ASH 2022 | Updates from ICARIA-MM: longer-term efficacy data on the combination of Isa-Pd in R/R myeloma

Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, MA, gives an update on the Phase III ICARIA-MM study (NCT02990338) investigating isatuximab plus pomalidomide and dexamethasone (Isa-Pd) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory (R/R) multiple myeloma. Overall, the analysis found that patients receiving Isa-Pd demonstrated an improved progression-free survival (PFS) and overall survival (OS). Dr Richardson also comments on the impact of subsequent therapies on patient outcomes, and the importance of using this data to better understand the sequencing of therapies in patients with R/R disease. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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Transcript (edited for clarity)

We presented an update on the long-term survival analysis, which encouragingly was positive in favor of the three drugs versus the two. But what we saw also in that analysis was the impact of bringing CD38-targeting therapy into the control arm appropriately as it should be, and how much of an impact that had on outcome. And when we corrected for that using a statistical technique, it was very interesting, because the hazard ratio improved as you would expect, but nonetheless helped with understanding the impact on survival benefit from the initial treatment with the triplet versus the doublet...

We presented an update on the long-term survival analysis, which encouragingly was positive in favor of the three drugs versus the two. But what we saw also in that analysis was the impact of bringing CD38-targeting therapy into the control arm appropriately as it should be, and how much of an impact that had on outcome. And when we corrected for that using a statistical technique, it was very interesting, because the hazard ratio improved as you would expect, but nonetheless helped with understanding the impact on survival benefit from the initial treatment with the triplet versus the doublet.

So ICARIA, just to remind our listeners, is basically isatuximab pom/dex versus pom/dex, there was a significant PFS benefit and now there’s a survival benefit. The issue we were presenting was how do you interpret sequencing of therapy, and how in the Phase III setting in relapsed/refractory disease do you interpret clinical benefit over the longer term?

And so while survival remains the gold standard appropriately, at the same time, understanding subsequent therapies and what they do is a particularly important area of research. So this is what we presented on, and we showed that using CD38-targeting therapy, even after the triplet had failed, the patient actually did [inaudible] some responses, especially when used in combination.

Conversely, interestingly, if you had the triplet and progressed, using chemotherapeutics such as alkylators was very important in restoring response. And interestingly, immunomodulatory therapy, either after pomalidomide or dexamethasone had failed the patient or isatuximab, pom/dex had failed the patient, the responses weren’t as good. So it helps you to understand what sequencing you should be looking at. And obviously with the excitement around BCMA, it’s clear. BCMA after CD38-targeting strategies fail would make good sense. And interestingly, it also showed that chemotherapy alkylation may be very important in selected patients, which pivots back to the original things we were discussing around melflufen, for example. So there’s lots of interesting data from this analysis.

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Disclosures

Regeneron: Consultancy; GlaxoSmithKline: Consultancy; Secura Bio: Consultancy; Protocol Intelligence: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Celgene/BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding.