EHA 2026 | Venetoclax combinations show high remission rates in FLT3- and IDH1-mutated AML

We have run a study at our institution where we have used the combination regimens involving venetoclax plus gilteritinib for FLT3 mutated patients and venetoclax plus ivosidenib for IDH1 mutated patients. We have combined these two targeted therapy drugs either as Ven-Gilt or Ven-Ivo with a combination of hypomethylating decitabine or azacitidine for frontline patients. For the relapsed refractory patients, we have used a different backbone. So for the fit patients, we used Van-Gilt plus low-dose cytarabine and actinomycin D. For relapsed refractory IDH1 mutated patients, we have used actinomycin D, low-dose cytarabine plus Ven plus Ivo, so a four-drug relapsed refractory salvage patient treatment. So what have we actually found? That these regimens were well-tolerated. For the fit patients, we have witnessed complete remission plus complete remission with incomplete platelet recovery rate, so a cumulative CR rate of 77%, which was slightly higher in the newly diagnosed patients. It was 72% in the relapsed refractory setting. These patients in the newly diagnosed cohort were elderly with a median age of 79 years old and a median ECOG of two, so weren’t really fit. And the relapsed refractory patients were slightly younger and slightly fitter. So we’ve enrolled 13 patients to the newly diagnosed cohort and 32 patients to their relapsed refractory, IDH1 pre-mutated cohort. And in those patients, we have seen the median overall survival of 15 months in the newly diagnosed and 18 months in the relapsed refractory patients. The main concern about the toxicity is, of course, myelosuppression, which we need to address. As we have used these combination regimens for FLT3-free patients with Ven and Gilt on an individualized basis, so we have reduced the dose individually on a case-by-case principle. If patients are having prolonged myelosuppression, we reduce the doses of Gilt and then usually from 14 days to seven days to have the lowest cumulative myelosuppression. So we’re happy about the FLT3-free patients; importantly, these regimens allowed a proportion of transplant-eligible patients to proceed to allogeneic stem cell transplantation. So that was 80% of relapsed refractory patients who were eligible for a transplant; they went on to a transplant, so a high bridge to transplant rate. A few patients in the newly diagnosed cohort, despite being older or less fit, they could also proceed to an allogeneic transplant. And in those patients who were allografted, the median overall survival is currently not reached. As for the IDH1 cohort, we had eight patients enrolled, five newly diagnosed and three relapsed refractory, and actually, the response rates are 100% in both newly diagnosed and relapsed refractory patients, and the median overall survival is currently not reached, and we have seen no relapses or deaths. This is a very good preliminary signal that the triplet with Ven-Ivo and HMA is actually very effective. We’re very happy that it is in line with the work presented here by MD Anderson’s group. So importantly, these IDH1 mutated patients also could proceed to an allogeneic transplant if they were eligible for that. So we’re really happy with this. I think the safety of the Van-Ivo combination produces less concerning signals regarding myelosuppression, as ivosidenib does not cause additional myelosuppression. As from our data, we see that. And the only treatment-emergent adverse event was QTcF prolongation, which was related to ivosidenib, but did not, it was in one case of a grade three event, but it did not cause an arrhythmic event.

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