At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Claire Harrison, MD, FRCP, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom, shared expert insight on the pooled analysis of phase 3 RESPONSE and RESPONSE 2 phase 3 trials that provided further evidence of the benefit of treatment with Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib for patients with polycythemia vera (PV), with or without splenomegaly.

Transcript:

Hello, my name is Claire Harrison. I'm a consultant hematologist working at Guy's and St. Thomas' hospitals in London, in the UK. I want to share with you today some data that we recently presented at the ASH 2023 meeting in San Diego concerning further information about ruxolitinib treatment in polycythemia vera patients, looking at a pooled analysis across the response studies.

These were the 2 studies that led to the approval of ruxolitinib for patients who have had an inadequate response or are intolerant of hydroxyurea, which is our most common therapy to treat patients worldwide with PV. In these studies, ruxolitinib was superior to a basket of best available therapies at providing hematocrit control, which is our key aim for PV patients, [and] controlling of other aspects of the blood count, such as white count and platelet count, as well as improving symptoms which can be very bothersome for these patients.

What we wanted to do and the data we presented in this poster came from both of the response studies. It's possible to do this because the studies had a very similar design. The main difference was there is a requirement for splenomegaly in response 1, but not in response 2. What was looked at was pooling the data from these studies, looking at patients who were originally assigned to ruxolitinib as well as crossover patients, looking at, again, the primary endpoint, hematocrit control, symptom control, but also what's recently come to the fore[front] in this field is the data with regard to looking at minimizing the amount of disease a patient has as assessed by looking at the JAK2 (V617F) allele burden.

As listeners will know, this is the [most common] mutation that we would see in 97% of PV patients. In this poster, we presented changes over time with the JAK2 allele burden from baseline out to week 208. the interest in this stems from a common interest in the myeloid field, but also as a result of an academic study, which we did in the UK called MAJIC-PV, which linked 50% reduction in JAK allele burden with improved overall progression-free survival, thrombosis, and myelofibrosis transformation-free survival for these patients.

What were the results? Overall, 371 patients were included in the analysis, and hematocrit control at week 28 and out to week 80 was better with ruxolitinib. We saw also 62% responses versus 18% responses, and out to week 80, we saw durability in this aspect by 47%, and nearly all patients in the control arm had crossed over because of failure of control. Also, importantly, we did look at symptom responses. Now, this is something we also looked at in the MAJIC study where we saw that symptom responses were durable for patients out to 4 years, even in a much smaller study.

But in the response pooling, we saw, again, durable symptom benefit as measured by 50% reduction in total symptom score. Now, concerning the JAK allele burden data, this is a really novel aspect of this poster, I think, and here we can see that responses in terms of reduction of the JAK allele burden were much better for ruxolitinib treated patients, even though the best available therapy included some patients that were treated with interferon, which, conventionally, we would regard as a drug that definitely reduces allele burden.

If you think about reducing to a target of less than 10%, which has been shown by colleagues in France to be linked to your ability to stop drug, that was achieved by 21% almost of patients in the ruxolitinib arm, 9% of patients in the crossover group, and 3.7 [%] in the back group.

[With] partial molecular response...this is a 50% reduction. This is the one that's linked to better outcomes for patients, was also achieved by between 35 and 40% of patients in the ruxolitinib arms and that was superior to those patients in the control arm. Amongst the patients overall in the control arm, the analysis is a little bit limited because of crossover, but again, this best decrease of between 25 to 50% reduction was seen in 7.2 for 25 and 2.6% of patients for best available therapy versus, as I said, the sort of 30 odd percent of patients with ruxolitinib.

So, this is some interesting data and it would be nice in the future to do a pooled analysis across the MAJIC-PV and response studies and really these provide further comprehensive evidence of the benefit of ruxolitinib in patients with PV who are failing a first-line therapy regardless of whether they have splenomegaly.

Source:

Harrison C, Kiladjian JJ, Palandri F, et al. Ruxolitinib treatment in polycythemia vera results in reduction in JAK2 allele burden in addition to improvement in hematocrit control and symptom burden. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 4553