ASCO24 Updates: Dr. Sankalp Arora on Azacitidine – Ruxolitinib Combination for High-Risk Myelofibrosis

The American Society of Clinical Oncology (ASCO) Annual Meeting is one of the largest and most prestigious conferences in the field of oncology. This year, the meeting took place from May 31 to June 4 in Chicago, Illinois. The event gathers oncologists, researchers, and healthcare professionals from around the world to discuss the latest advancements in cancer research, treatment, and patient care. Keynote sessions, research presentations, and panel discussions are typically part of the agenda, providing attendees with valuable insights into emerging trends and innovations in oncology.

This year, OncoDaily was at ASCO 2024 for the first time covering the meeting on-site. We had the pleasure of interviewing researchers who summarized the highlights of their work.

In this video, Sankalp Arora from MD Anderson Cancer Center shares insights on ‘Long term follow-up results of phase II clinical trial evaluating ruxolitinib (RUX) and azacitidine (AZA) combination therapy in patients (pts) with myelofibrosis’

Good afternoon, my name is Sankalp Arora. I am currently a first year HEMONC fellow at MD Anderson Cancer Center in Houston. It is my pleasure to be talking about my abstract here at ASCO.

So the study that I’m presenting here is looking at long-term follow-up of using the Azacitidine ruxolitinib combination in patients with myelofibrosis. So it’s well known that JAK inhibitors monotherapy such as Ruxolitinib monotherapy is effective in myelofibrosis, particularly in reducing the spleen size and patient symptom burden. However, that efficacy is limited somewhat and it’s unclear whether it has any disease modifying effects or does it really alter the natural disease course history in myelofibrosis and so far stem cell transplant has remained the only curative option in myelofibrosis.

So this area has been a heavy area for research in terms of new drugs or new combinations that can help increase or enhance the efficacy with JAK inhibitors and so in this period we had this clinical trial looking at combining ruxolitinib with the hypomethylating agent azacytidine in patients with myelofibrosis. So this was a phase two trial conducted at MD Anderson Cancer Center in Houston. We enrolled patients more than 18 years of age who had primary or secondary myelofibrosis with intermediate one, two or high risk disease by DIPS criteria.

The primary outcome of the study was looking at response rate per the IWG MRT response criteria, looking at the clinical reduction in palpable spleen size below the left costal margin and reduction in symptom burden which was using the total symptom score per the MP and SAF criteria. The other endpoints were looking at survival and adverse effects and safety data. So total we enrolled 61 patients in this final presentation of the study and the 61 patients here it’s very important to know that 62 percent of this patient population was actually intermediate to or high risk disease.

So this was more higher risk cohort than what we’ve seen in prior studies and around 14 patients that is 23 percent of our cohort actually had more than five percent bone marrow blast at baseline. So and as you know that this particular group with higher bone marrow blasts are often excluded from the prior RUX monotherapy trial. So we overall had a higher risk cohort going ahead and so out of these 61 patients we saw at least one IWG MRT response in about 45 patients accounting for an overall response rate of 74 percent.

Breaking down the responses majority of the improvements were seen a majority of the responses were improvement in symptom burden so the TSS 50 score that is 50 percent reduction in the total symptom score for patients who had baseline TSS 12 or more and that was seen in 69 percent of the patient population by the last median follow up by the last follow up.

Similarly in patients whose baseline spleen size was at least five centimeters or more below the left costal margin we had 61 percent of the patients having achieved 50 percent reduction in the spleen size so a CI spleen of 61 percent. These are pretty impressive numbers given the high risk cohort that we already have.

We also had four patients achieve complete cytogenetic remission and four patients achieve partial molecular response in their JAK2 allelic burden in the study as well. Looking at overall survival with the median follow up of about 92 months we had an overall median OS of 46 months with a three year survival rate of 60 percent. It’s interesting to know that about five patients that had eight percent of the population did transform to AML during the study but three out of these five patients already had bone marrow blast more than five percent at baseline.

At the end of follow up by data cut off period about 14 patients that is 23 percent of the population has transformed into AML but this is at the latest median follow up. In terms of transplantation so 20 or 33 percent of the patient population that is 20 patients were able to be bridged to allergenic stem cell transplant and on a landmark analysis we found that patients with intermediate to or high risk disease who underwent transplant in our cohort had a trend towards improved median OS even though statistical significance was not achieved.

In terms of the safety data the side effects that we saw were quite expected with ruxolitinib and azacitidine individually.

So it was mostly hematologic side effects the most common grade three to five treatment emergent adverse effects were basically anemia and thrombocytopenia. We also had pneumonia seen in around 20 percent of the patient population. Most of the side effects were manageable and transient and only four patients had to be taken off of study because of severe side effects and these included anemia thrombocytopenia and neutropenia.

So in conclusion we would say that the azacitidine ruxolitinib combination has been shown to be effective in our cohort which included 62 percent patients with intermediate to or high risk Dibbs disease and with around 23 percent patients having more than five percent bone marrow blast and baseline.

So this is the numbers that we saw in total symptom burden TSS 50 reduction and spleen size reduction are actually higher compared to those seen in rux monotherapy trials such as the jump trials or the comfort studies. Again this was a single arm trial so we technically cannot compare across different studies but if you were to look at historical controls we see a better response rate.

We think that this might be a particularly good option in patients who have high risk Dibbs disease or increased number of blasts at baseline.

More videos and content from ASCO 2024 on OncoDaily.