Texas MPN Workshop 2021 | Looking beyond JAK inhibitors: novel targeted therapies and strategies for MPN treatment

Thank you so much for allowing me to speak about this topic of novel targeted therapies beyond JAK inhibitors in patients with MPNs, in particular, myelofibrosis. I’m really honored to be joined by my co-founders and colleagues, Dr Ruben Mesa and Dr Srdan Verstovsek to found the Texas MPN workshop. This will be our second annual get together virtually, of course, during the extended pandemic time. Really, what I’m seeking to highlight is that there is an explosion of Phase II and Phase III investigational clinical trials that have really blossomed in just the last few years, so just before the pandemic and fortunately, continuing during.

I think basically, the excitement for all of us for our patients and caregivers is really threefold. One is that you have brand new JAK inhibitors beyond the two currently available, that is ruxolitinib and fedratinib. So, a host of new drugs, pacritinib, momelotinib, jaktinib and others that we heard data on in the last few meetings.

A second category of excitement is that of add-on or add-back strategies where you take a novel agent such as navitoclax or the bromodomain inhibitor from Constellation, now known as pelabresib and add it on to the JAK inhibitor and for a combinatorial approach in those patients who are suboptimal are actually failing the JAK inhibitor.

Then finally, there’s a whole new area of completely novel agents that do not rely on JAK/STAT pathway inhibition, or the combinatorial approach with the JAK inhibitor, so just completely brand-new agents on their own. Drugs such as the imetelstat telomerase inhibitor, LSD-1 inhibition, so on and so forth. Again, we’ve seen a lot of these trials now in the Phase II, starting to enter into randomized Phase III settings, which is a brand-new territory for our field. You’re talking about more than 10 to 12 of these in active development at this time, so that’s really, really big.

I think one more aspect of this is starting to think about, for the first time, dual oral therapy, so adherence to not just one oral therapy, but two, overlapping and non-overlapping toxicities. Thinking about thrombocytopenia, GI side effects, fatigue, dropping of the blood counts initially, so increased follow-up visits. Then of course, looking out for new markers that may be the second drug or the new drug can add. Are they reducing bone marrow fibrosis? What’s going on with the allele burden? Cytokine correlation? Overall survival? Symptom burden? MPN symptom? Burden benefits? A whole host of new questions, a whole host of new issues that have really arisen, I think in a good way overall for our field and for our patients, to not only give patients more options for therapy, but also to address the urgent unmet medical needs. Those patients with low platelets, low hemoglobin, large spleens despite JAK inhibitor, poor overall survivals, maybe high-risk molecular mutations. Really, a brand new, whole new era in MPN and targeted therapies, all of which are moving beyond JAK mono therapy inhibition.