VIDEO: Recent developments in myeloproliferative neoplasms

Editor’s note: This is an automatically generated transcript. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

So, a lot of things right. I think the field of myeloproliferative neoplasms has moved pretty nicely over the last couple of decades since the first identification of JAK2 mutation, followed by CALR and MPL and subsequently then identifying other non-driver somatic mutations which we know drive the disease pace or drive the acceleration of the disease. That has helped us identify pathways beyond JAK/STAT pathways. Ultimately, all of that has led to identifying different agents or novel agents that can target those pathways outside of JAK inhibitors, which have traditionally been the mainstay of treatment.

Some of the major things in the pipeline that have moved long over the last few years now have been combination therapies, combinations with JAK inhibitors in a relapsed refractory setting, meaning patients who do not have a great response to frontline JAK inhibitors. And also in an upfront setting, so those recently with the navitoclax trial that was presented at ASH and pelabresib trial that was also presented at ASH and then again at ASCO. And we're awaiting publications for both of those, and kind of trying to understand what the what the fate of each of those products is going to look like.

There are other products in upfront combination studies like selinexor, which has a pretty impressive spleen response in the early data. So, all of those together are generating some excitement in terms of how the treatment landscape of myelofibrosis is going to look like. This is especially important in a relapsed refractory setting meaning patients who are not deriving as much benefit from JAK inhibitors upfront pertaining to, for example, spleen and symptoms and other things. And one of the trials that is on its way to opening is the trial of navtemadlin which combines navtemadlin to ruxolitinib in patients who are not having a good response to upfront ruxolitinib.

The other field or the other area where novel agents in MPNs are starting to enter now is targeted therapy in the form of antibodies and BiTEs, one of which is a CALR-directed or mutant CALR-directed strategy using monoclonal antibody or even a BiTEs that's in process of development. Those are exciting to the field because this is the first time we're actually targeting the mutation and trying to develop a strategy specifically for mutant CALRs specifically for one of these driver mutations. And lastly, I think the role of transplant continues to evolve in the scope of myelofibrosis there's, there's more data that is published in terms of conditioning regimens we’re in process of publishing our donor paper using the CIBMTR data. So, I think all of those together are kind of just hold somebody evolving the scope of model fibrosis treatments.