Managing Editor, OncLive®
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource Contagion, strengthened the Rare Disease Report, of HCPLive, and now serves as the main digital news writer for OncLive. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: firstname.lastname@example.org
James M. Rossetti, DO, discusses strategies for symptom management, tools available for risk stratification, and updated data with some of the pivotal agents in myeloproliferative neoplasms.
James M. Rossetti, DO
When it comes to the treatment of patients with myeloproliferative neoplasms (MPNs), assessing for potential disease-related symptoms is key, said James M. Rossetti, DO. Moreover, risk stratification in all of the diseases as it relates to blood cancer is of the utmost importance in order to identify who may require more aggressive therapy.
“We have had a lot of new agents available to us over the past few years. It's an exciting time in the treatment of MPNs,” said Rossetti. “Some of the long-term follow-up data that we have with some of the agents that are available I believe will help [healthcare providers] in the community feel more comfortable utilizing them.”
In an interview during the 2019 OncLive® State of the Science Summit™ on Hematologic Malignancies, Rossetti discussed strategies for symptom management, tools available for risk stratification, and updated data with some of the pivotal agents in the space.
OncLive: What are some of the key highlights in MPN treatment?
Rossetti: Symptom management [is key], which is really assessing our patients and better help them as it relates to their symptoms. The other thing that is important is risk stratification in all of the diseases that we treat as it relates to blood cancer. We’ve certainly come a long way in identifying those patients who are at greater risk and who might need more aggressive therapy, and we also know that there is a lot of work to be done. We've made great progress and we have some clinical trials that are very exciting.
What is important to keep in mind in terms of symptom management?
Symptom management largely relates to the disease that the person has. We really need to assess our patients and do a better job at understanding which symptoms might be related to the disease. Many patients with myeloproliferative disease will tell you that they feel as if they're ignored for a period of many years with vague symptoms. If everything else has been excluded, even in a low-risk patient, I believe that we have to accept and appreciate the fact that the disease can cause significant symptoms by way of cytokine release and others.
We do have decent symptom management available to us; some of the agents that are available, such as ruxolitinib (Jakafi), have really helped a significant number of our patients symptomatically. With myelofibrosis, we're certainly learning more about that agent in polycythemia vera (PV) as well. Aspirin, which is certainly one of the age-old drugs, can manage many symptoms as well. However, even there, looking at other antiplatelet therapies, and importantly, looking at new agents might help these patients as well.
In terms of risk stratification, what tools are you using to assess for risk?
We need to really be able to assess what our patients are experiencing. Take PV; it's very important that we assess past events with greater care, such as cardiovascular risk factors. It's easy for us to ask if [patients have] had a pulmonary embolism, but not so much to assess other risk factors that they might have that increase their risk for thrombosis. We include in that model molecular profiling, as it relates to risk for transformation, and as it relates to risk for thrombosis. We include all of these things, and, of course, the blood counts and cytogenetic modeling and I believe we are getting better.
Take myelofibrosis; we use the Dynamic International Prognostic Scoring System plus score frequently and all of these new evolving models, but we're learning more about how to integrate all of that information into a more cogent way of assessing risk associated with our patients. It’s very important because despite the fact that we do a decent job and we're doing better and better, we probably still [do not properly risk stratify] a significant number of patients.
What important long-term follow-up data have recently read out in the space?
I believe, at least with ruxolitinib, many clinicians in the community have been reluctant to utilize ruxolitinib relatively early because we didn't have the long-term data available to us that we have for other agents, such as hydroxyurea, busulfan, and others out there. As these data mature, people will become more comfortable or they won't, depending on the long-term data. Thus far, however, I believe [the data are] very encouraging.
Fedratinib was recently granted priority review status by the FDA. If approved, what kind of impact could that agent have in myelofibrosis?
I believe [this agent] will have a significant impact. With all of these drugs, one of the things that we ultimately see happening is reluctance early on; I believe ruxolitinib experienced that tremendously. We know that there are some limitations of the agent. However, again, I believe some of those limitations are wearing off as data are maturing.
The same thing is going to happen with fedratinib; that's the bottom line. The more agents we have, we go through that period of experience, and of commercial experience, for our patients and God willing it makes a difference.
What are your thoughts on momelotinib? It has been granted fast track designation, but there are mixed data.
Again, one of the concerns that I always have with all of these agents is dismissing them too early. Oftentimes, that's [that is due to the] design of a trial. Other times, it's not so much related to the design of a trial but maybe the wrong patient population.
In this group of patients in particular, it's very difficult to study, in part because everyone is so heterogeneous. That makes an analysis of data a bit more difficult. Long-term follow-up becomes the key. However, I do believe that responsible use of these agents that get to market is what's going to make a difference in the long-run. This is because it's very, very hard to prove long-term benefit with small clinical trials.
Will there continue to be a role for interferon in MPNs?
I believe so, especially in younger patients; that is really the population. Many of us who do use interferon aren't as afraid of it; [perhaps we start at lower doses to better manage adverse events], but I believe there is always going to be a population of individuals who benefit from interferon. Therefore, I don't think we should ignore it.
What ongoing research at University of Pittsburgh would you like to highlight?
One of the things that we're looking at is a lysine-specific demethylase inhibitor. We're very excited. We're just opening that clinical trial, which is looking at patients who have failed or were intolerant to ruxolitinib or JAK inhibition.
One of the things that we're excited about with that particular molecule is that, like ruxolitinib and the other agents, it's oral. The early data looking at symptom management [showed] splenic size reduction and perhaps even improvement in bone marrow fibrosis. These are early data, to be sure, but they are enough to spur us forward with further investigation.