SOHO 2025 | Early intervention with IDH inhibitors in IDH-mutated MDS: insights from clinical experience

So we have approval of ivosidenib for IDH1 relapsed/refractory patients. Now this has predominantly been used in patients that are either HMA failure, chemo exposed, clearly high risk. But the question is if we intervene early, can this potentially change the natural history of the disease? And we published a little while back that particularly in lower-risk myelodysplastic syndromes that patients with IDH mutations present with severe neutropenia and there’s really very little of any therapy that can ameliorate that so I’d say now actually maybe dating back around seven years we’ve started to incorporate frontline IDH inhibitors I’d say more ivosidenib but some enasidenib as well and actually we’ve had essentially a hundred percent response rate my farthest patient is over six years with perfectly normal counts, we’ve typically seen rapid resolution of the neutropenia but most of these patients have had mild other cytopenias and those have also you know normalized and this seems to be way better than what we would expect in in relapsed/refractory MDS or AML. And so perhaps if we intervene earliest that’s the time point that we can really prevent the disease from ever changing now these are small numbers, ultra rare patients I think if people remember it took over almost you know over five years of time and only 17 patients to get the IDH1 label in relapsed/refractory MDS. Now I think going along with this, Kelly Bolton at WashU has been leading a CCUS trial. So IDH1 mutation with CCUS were a part of this. So I’d be looking to data at ASH because I think this will even greater help solidify if we intervene early, our response rates better and ideally more durable. But toxicity is essentially zero in this upfront setting and very excited by the results to date.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.