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Hello, my name is Srdan Verstovsek, professor of medicine in the leukemia department at MD Anderson Cancer Center in Houston, Texas. I'm going to summarize the highlights of MPN; this is myeloproliferative neoplasm topics from ASH 2017 that was just held in Atlanta, Georgia. He picked seven clinically relevant abstracts and presentations that may have influenced how we manage patients with MPN today in our everyday clinic.
The first one is from Dr. Grunwald. Dr. Grunwald has presented the results from a REVEAL study; this is a patient reported symptom burden, and peripheral blood count findings from patients with polycythemia vera as it's observed in a clinical setting from multiple different clinical settings in the United States. Approximately half of the available patients, it was surprising to me, had achieved a hematocrit below 45%, but no more than half. And only a quarter had achieved a complete hematological response based on controlled hematocrit vitals and platelets. With the exception of pruritus, patients reported similar symptoms ... similar symptom control, regardless of blood count control, which may suggest symptom burden in patients with PV can't possess this despite blood control. This study highlights the importance of a regular symptom assessment during the usual care of patients with PV, which is a central component of the recently published NCCN guidelines for PV.
When it comes to choice of therapy for polycythemia vera patients, as well as for patients with essential thrombocythemia, Dr. Yakoub has presented interesting results, and the final results of a study that was done in NPN consults here in the United States and globally, on a use of interferon, the alone acting interferon pegylated interferon-alpha-2a. Interferon acting agents in PV and ET, and they even can in pro-bone marrow biopsies in some patients, or bone marrow appearance in some patients, as well as decrease or sometimes, even eliminate the cells with the molecular findings, the JAK2 positive cells in some patients may go away on therapy with interferons. The primary endpoint of this study was assessment of clinical benefits of this medication, also known as Pegasus, in patients with ET and PV that are high risk, after a failure of hydroxyurea. In a majority of the patients, the therapy with Pegasus was successful in achieving study goals, controlling the blood cell count as well as improving symptoms and preventing progression of splenomegaly. On the face value of toxicities, we have some sense that this medication, because it's less frequently given, may have improved toxicity profile than medications of similar nature, interferons that are given three or five times a week.
In addition, we have another therapy that was recently approved as a therapy for polycythemia vera, in a second line setting. Dr. Kiladjian from France has reported a two hundred and eight week follow up of a response study. This study was a phase three study comparing ruxolitinib` to base value therapy in patients with polycythemia that were intolerant or resistant, or failed to respond to hydroxyurea. A long-term follow up of this study showed significant durability of a response in controlling hematocrit levels, as expected with this medication from historical experience in myelofibrosis. The adverse event profile was excellent, with no new toxicities determined, indicating that this therapy is safe and effective long-term. Observation of the safety included assessment of any thromboembolic adverse events, which was very low, giving us assurance that we controlled the assigned symptoms of the disease, PV, in this case. We can possibly even decrease the thromboembolic events, which is the ultimate goal of therapy in PV.
On the other hand, a report from the New York showed that ... as it was known before in myelofibrosis setting, ruxolitinib may suppress to some degree immunological system, and predispose patients to atypical infections. Dr. Ritchie presented these results in a poster session, saying that there is a slight increase in infections in patients on ruxolitinib compared to those that are not, particularly atypical infections. And there is a suggestion of increased risk of secondary cancer, particularly secondary skin cancer.
Now we move to myelofibrosis. Dr. Vannucchi presented a new proposal for assessment of a risk of dying in patients with myelofibrosis. So called "MIPSS70", which is mutation enhanced prognosis system for transplant patients with primary myelofibrosis, combining molecular findings along with standard clinical observations from a blood cell count and symptoms. The investigators were able to propose what they perceive as an improvement in our ability to prognosticate and properly refer patients to a transplant. MIPSS70+ is additional information on the same presentation where with the additional of a cytogenetic abnormality, we can even improve on the molecularly enhanced assessment too.
Dr. Masarova has presented interesting observation of a difference in myelofibrosis patients in chronic phase, whether they had a chronic phase with low blast, which is defined by up to 5%, or elevated blast in a chronic phase, which is now defined as a 5-9% of blast in blood or bone marrow. What is interesting to see is that the patients with chronic phase and elevated blasts had a worse outcome than those with low blasts. And similar to that with accelerated phase, which is very, very established group of patients that have a blast between 10-20%. In addition, the group of patients with elevated blasts, again 5-9%, have a high risk of progression to acute myeloleukemia, than those with low blasts. Finally, the use of ruxolitinib, which has been shown to prolong survival in patients with myelofibrosis, was equally effective at prolonging survival in patients with low blasts and high blasts as long as they were in a chronic phase.
Finally, Dr. Al-Ali has presented on a very large observational study called JUMP study, which was a phase three B study, expanded axis study of ruxolitinib in patients with myelofibrosis around the globe. More than 2200 patients with myelofibrosis were treated. This study showed that indeed, ruxolitinib is very effective in patients with high risk and intermediate risk myelofibrosis patients in controlling symptoms and signs of the disease. But has also shown that the therapy is equally effective in patients with intermediate one prognosis calling system. Therefore, it is valid to treat patients with ruxolitinib that have myelofibrosis, regardless of their risk of dying.
My closing comments are listing on this last slide, where I take several points from my short presentation ... selected presentation on myeloproliferative neoplasms here at ASH 2017. Management of PV in community practice appears not to be optimal. This relates to uncontrolled blood cell count, but also to inadequate control of PV related symptoms. Long Acting interferon may have a role in a second line therapy for patients with high risk ET and PV not doing very well on hydroxyurea. Ruxolitinib has been approved as therapy in this setting, in polycythemia vera, for second line. And now we know that its benefit is durable and safe. One however needs to be aware of sporadic, atypical infections, or a skin cancer risk.
New clinical molecular prognosis score for myelofibrosis has been proposed, combination of a molecular finding and even cytogenetic findings with a classic prognostic scoring system is proposed, and is perhaps useful in everyday practice. We also know that the blast on its own, the presence of blast in the blood or bone marrow in myelofibrosis has a significance, and we now learn about a group of patients called chronic phase with elevated blast that have a 5-9% blast in the bone and bone marrow with an increased risk of AML transformation, and survival in myelofibrosis. But ruxolitinib appears to be able to prolong life in this setting as well. The efficacy of ruxolitinib has been confirmed in a very large level study called JUMP study, in more than 2200 myelofibrosis patients, that included not only high risk and intermediate risk patients, but also intermediate one risk patients, suggesting that ruxolitinib should be used regardless of risk of dying for patients that have symptomatic splenomegaly or suffer from myelofibrosis related symptoms. Thank you.