ASCO 2024 | A Phase II trial of ruxolitinib and azacitidine combination therapy in patients with myelofibrosis

I’m excited to present this data at ASCO this year. And this is basically a phase two clinical trial, as you said, looking at combining ruxolitinib with azacitidine in myelofibrosis. We know that ruxolitinib and other JAK inhibitors have efficacy in myelofibrosis and they especially help in reducing symptom burden and spleen size. But monotherapy with JAK inhibitors doesn’t seem to really affect the disease course. And this area in myelofibrosis has been an area of active research trying to find therapies which can actually slow the disease course and impact survival. So based on that, we had this combination trial at MD Anderson. We had a total of 61 patients that were enrolled in the trial. Interestingly, majority of them, 62% had intermediate two to high risk disease. And so this was historically more high risk disease compared to the rux monotherapy trials. Also, around 14 patients, 23% of the patient population had bone marrow blasts, more than 5% at diagnosis. This is actually a group that’s often excluded from rux monotherapy trials because they are so high risk. So we had an overall high risk group of these 61 patients.

The primary endpoint was looking at the response rate for the IWG-MRT criteria. And we saw at least one response in 45 out of the 61 patients around, with an overall response rate of 74%. Most of the responses were a reduction in spleen size, palpable spleen size below the left costal margin, which was around 61% patients and 69% patients had a 50% reduction in their total symptom score. This accounted for most of the responses we had. Some patients, like four patients, had complete cytogenetic remission and four patients had partial JAK2 molecular response. So partial reduction in the allelic burden by 50%. In terms of the survival, the median overall survival of the cohort was around 46 months after a median follow up period of 92 months. We did see that patients with intermediate two to high risk disease who underwent an allogenic stem cell transplant had a trend towards improved median overall survival compared to the patients who did not undergo transplant. So again, showing that transplant continues to have an active role in myelofibrosis.

In terms of the safety data, it was expected. Side effects with azacitidine and ruxolitinib most common grade 3 to 4 3 to 5 adverse events were basically anemia, thrombocytopenia, and pneumonia. Most of these effects were transient though, and only four patients had to be taken off trial because of severe toxicity, which was again anemia, thrombocytopenia, and neutropenia. So I think in conclusion, this is a very effective combination for myelofibrosis, especially those with high risk features at onset. So bone marrow blasts elevated at diagnosis or high risk features.