Durability, Transfusion Independence Achieved With IDH1 Inhibition in MDS

Justin Watts, MD, associate professor in the hematology division at Sylvester Comprehensive Cancer Center and part of the University of Miami Miller School of Medicine in Florida, discusses a study of olutasidenib (Rezlidhia) in patients with IDH1-mutated myelodysplastic syndrome (MDS).

According to Watts, the phase 1/2 study (NCT02719574) included a cohort of 22 patients who generally had higher-risk MDS who were treated with olutasidenib alone or in combination with standard therapy. The outcome of a 59% overall response rate (ORR) and 27-month median overall survival (OS) were greater than would be expected with azacitidine or other hypomethylating agent (HMA).

The favorable OS represented both long durations of response to treatment as well as olutasidenib contributing to transfusion independence or maintenance of transfusion independence in other patients who did not respond completely, Watts explains. This could be seen even in patients with relapsed/refractory disease. Considering poor historical outcomes for these high-risk patients and lack of myelosuppression associated with the IDH1 inhibitor, these were encouraging findings for this therapy, he says.

TRANSCRIPTION:

0:10 | This was a very high-risk MDS population. There were no low-risk patients, and there were only a couple of intermediate-risk patients. Eighty-six percent of the 22 patients were high or very high risk, and some even had [acute myeloid leukemia] by new criteria like the International Consensus Classification. That being said, what we have seen in AML is that the patients who do very well tend to have lower blast counts and fewer mutations and lack of signaling pathway mutations—more resembling MDS, just their blasts are over 20%. So we weren’t surprised to see that these patients with MDS overall did very well with a 60% ORR in a mixed population, which…is greater than expected with standard-of-care azacitidine, or HMA alone, using a targeted therapy in both a single-agent and combination setting.¹

1:14 | The OS was equally impressive, and I think that’s due to both duration of response in the responders and the achievement of transfusion independence even in patients who don’t have a full complete response [CR] or an optimal response, which is also very important for long-term outcomes. There was notable achievement of transfusion independence, or maintenance of transfusion independence if they were independent at baseline on the study, a real lack of myelosuppression, and the [median] OS was around 27 months for the entire population.… But even when you looked at the relapsed/refractory [patients], who historically have OS on the order of 5 or 6 months, it was over 16 months in this group. So that was very encouraging.