ASH 2020 | Prof. Ruben Mesa: The latest research progress in MPN field, and How should disease-related care for MPN patients are managed in this phenomenon?

Editor's note: For the first time, the 62nd annual meeting of the American Society of Hematology (ASH) was held online December 5-8, but even so, there was plenty of attention for the blockbuster blood research.Oncology Frontier invited Prof.Ruben Mesa, from UT Health San Antonio MD Anderson Cancer Center, to share decades of valuable experience for the career development and planning of young doctors, and asked him to summarize the latest developments and hot research in the field of myeloproliferative diseases (MPN) at this conference. Prof. Mesa also shared with us how to manage and treat patients with myeloproliferative disease (MPN) in an epidemic situation.

Oncology Frontier: Could you please give advice for junior hematologist on early career stage? 

Dr Mesa: For the individual at the beginning of their career as a hematologist, I think there are two things that are very important. First is to develop a deep level of expertise in one aspect of hematology care. It is good to be involved with the care of a range of patients, but have one area that you can really take ownership of. Go to those meetings. Connect with people. Understand the issues at play. Even if you have a lab, build on having enough clinical experience in caring for that group of patients to possess the clinical expertise to be able to bring to either your lab or your clinical research. The second is to find a specific area to work on and to find good mentorship. It is not uncommon that during training, individuals will do projects in a range of areas - lymphoma, myeloma, leukemia, benign hematology. All research experiences are valuable. But I do think it is important to have focus if you are going to make progress. In my career, I have focused on myeloproliferative neoplasms and myelofibrosis. I was able to make progress both because I had very good mentorship from many at the Mayo Clinic, especially Ayalew Tefferi, but also because I focused on one area as opposed to trying to do many. That allowed me to get to know people, understand the diseases, care for those patients, become an expert who could receive referrals, and speak with authority in the design and conduct of clinical trial.

 

Oncology Frontier: Could you give some practical suggestions for new mentors?

Dr Mesa: Being a mentor is a great responsibility. You play a key role in helping develop a junior faculty member. One thing we learn about mentorship is that mentors also need mentors. You are mentoring individuals up-and-coming in their careers, maybe in one aspect of their career or maybe in several aspects, but we too have mentors. People have mentored us. There are people who are good mentors, from whom we learn how to be a good mentor. That can include understanding how to best communicate with mentees, setting plans and priorities, understanding what responsibilities to give to the mentee to hold them accountable, and to have clear timelines/deadlines in terms of the projects mentees undertake. The process of mentorship is about helping them to become an independent investigator, as well as helping them to move to the next level of career development. Don’t think you have to learn this on your own. There are good mentors out there, and learning from them can help augment your skills as a mentor.

 

Oncology Frontier: At the ASH meeting, we’ve seen a lot of thematic sessions, Could you please highlight the impressive studies on the MPN  released in ASH? 

Dr Mesa: Many important advances were discussed for myeloproliferative neoplasms (MPN). If I try to summarize them, we have seen a reinforcement that there are multiple drugs that may improve survival in myelofibrosis. We saw from Dr Verstovsek from the MD Anderson group that the survival over the past decade for patients with myelofibrosis is probably improved by the favorable impact of JAK inhibition. We saw data suggesting that imetelstat, a new telomerase inhibitor, may impact survival in a favorable way in patients with myelofibrosis. And we saw that momelotinib, in longer term data from the phase III studies, likely benefits survival. These are really the first solid indications that not only one, but multiple lines of pharmacological therapy may have a favorable impact on survival in myelofibrosis. Next we saw there is a robust pipeline of new therapies for myelofibrosis in development. The BET inhibitor, CPI-0610. The LSD1 inhibitor, IMG-7289. The BCL2 inhibitor, navitoclax. Imetelstat, and many others also in development. But these four, both as combination therapies in JAK inhibitor naive patients (CPI-0610, and forthcoming data with navitoclax), as the addition of CPI-0610 or navitoclax to ruxolitinib to augment response, or all four of these agents as second-line therapies. All are incredibly important options. Third, we saw advances for patients with polycythemia vera, first with low-risk disease, potentially with the use of ropeginterferon, superior to phlebotomy potentially for low-risk patients, as well as the hepcidin mimetic, PTG-300, to simulate iron deficiency to aid individuals becoming phlebotomy independent. Finally, we saw multiple abstracts highlighting the benefits of interferons - both long-acting interferons like ropeginterferon, and pegylated interferon alpha-2a, in terms of achieving a complete hematologic response, decreasing the risk of thrombosis or bleeding, as a well as potentially having more long-term disease control.

 

Oncology Frontier:  The COVID pandemic has resulted in significant changes in many aspects of daily living. Does it have a significant impact on MPN patients? How should disease-related care for MPN patients are managed in this pandemic? Do you have any suggestions on it? 

Dr Mesa: This is an excellent question. First I would say that the COVID pandemic has shown us how close we are as a global community. When the pandemic really started to become a major issue in February and March, I reached out to our colleagues in Wuhan, China, in Italy, in New York and other parts of the US, and we have stayed in very close contact. There have been a whole range of communications and studies looking at outcomes and providing guidance to patients. We have seen that MPN patients don’t seem to necessarily be at a higher risk of acquiring COVID infection. However, in the early part of the pandemic, there were individuals with myelofibrosis in particular who seemed to have a more difficult disease course. These data specifically came out of Italy. My understanding is that the data from China was not as adverse for MPN patients, but Italy was very challenged. As our colleagues in Italy, Dr Tiziano Barbui and others, looked at these experiences, they identified that part of the challenge had been if individuals had been on JAK inhibition with ruxolitinib. When it was discontinued abruptly, this led to a worse outcome for patients, in that the JAK inhibition was likely decreasing inflammation in these patients, and disinhibiting cytokines by pulling back on the ruxolitinib might have aggravated any infection-associated pneumonia these patients were facing. We have recommendations on the ASH website for MPN patients. We have recommended that patients should be treated as they would be normally, but to be particularly mindful of the risk of thrombotic complications if they develop COVID. Secondly, do not delay the appropriate initiation of therapy. And third, if patients are on ruxolitinib and JAK inhibition, try to avoid cessation of the medicine in the setting of COVID infection unless it is clinically indicated. Ruxolitinib has shown activity against COVID-related pneumonia and has been in phase III clinical trials as a therapy to decrease the severity of COVID-related pneumonia, so there is a potential value to the medicine.