Texas MPN Workshop 2021 | Pros and cons of ruxolitinib for the treatment of MPNs

Well, thank you for inviting me and thank you for that great question. Definitely there are a lot of pros and cons with ruxolitinib. First of all, the pros. Well, it was shown to be efficacious with respect to reducing spleen size and symptom burden in two large, randomized, prospective, Phase II trials; the COMFORT-I and COMFORT-II study; and those COMFORT studies ultimately led to the approval of ruxolitinib for the treatment of myelofibrosis, at least to intermediate and high-risk myelofibrosis. Moreover, in a pooled analysis done of those two studies, with the long-term follow-up data, there was a survival advantage for patients randomized to ruxolitinib versus the other therapies, the control arms, in those studies. Again, how much survival advantage is unclear because there was crossover in those studies, but clearly there is a survival advantage for people who take ruxolitinib.

We know that ruxolitinib doesn’t really kill myelofibrosis cells, or eliminates them from the bone marrow, or reverses scar tissue regularly. So, we often think about this as people are living longer because they are living better: fewer symptoms, better nutrition, smaller spleen size, that people are more active, have better performance status. There’s probably also something to having lowered cytokine levels over time, and the stress on the body that that can do. So, I think all in all, ruxolitinib has really been a huge sea change in the treatment of myelofibrosis. Prior to that, there were no treatments.

I think the strongest evidence actually, is more on a population basis, and that was presented at the most recent ASH annual meeting, by Dr Verstovsek, and it’s a real-world analysis of patients with myelofibrosis before the approval of ruxolitinib, and after the approval ruxolitinib. So, we saw a huge jump in survival in patients diagnosed with myelofibrosis after ruxolitinib was approved in 2011. Moreover, it wasn’t just people who got ruxolitinib after the approval, their survival was better, but it’s actually people who didn’t even get ruxolitinib, their survival was better, and that means a couple of things in all likelihood.

It means that there’s better awareness of myelofibrosis, and we’re probably diagnosing many more people, because now there is a drug to treat this disease with. Secondly, I think it’s also improved our ability to deliver supportive cares, and it’s also spurred on lots of new clinical trials, so we’re always offering new therapies to patients via clinical trials, trying to push those envelopes and get new treatments out there, and thus people are living better. So again, ruxolitinib has been kind of a sea change in the field.

There are a lot of downsides. It doesn’t work forever; invariably there’ll be some point where the disease comes back, or changes, in spite of the ruxolitinib. And we know that survival after ruxolitinib, for patients with myelofibrosis, is very short. There’ve been a number of analyses published showing the median survivals of well under two years, closer to one year, in most patients. A lot of this has to do with clonal evolution too. We see changes in the chromosomes, or changes in the [inaudible], and the number of mutations that there are within the myelofibrosis cells that’s often driving that change in progression. And at that point, the patient’s condition can deteriorate rapidly, unless they undergo transplantation. So again, for those who cannot undergo transplantation, we’re always looking for new therapies and to move the field forward.