NASEEMA GANGAT (ROCHESTER)
POLYCYTHEMIA VERA
Polycythemia vera (PV) is a myeloproliferative neoplasm, with JAK2 mutation (JAK2V617F or
exon 12) as its hallmark. On next generation sequencing studies other frequently occurring
mutations include TET2 (22%) and ASXL1(12%). Additionally, PV is characterized by a
subnormal erythropoietin (EPO) level. Based on these findings, the diagnostic evaluation rests
on peripheral blood JAK2V617F screening coupled with EPO measurement. A bone marrow
biopsy is not mandatory to establish the diagnosis but recommended to help confirm the
diagnosis. Once diagnosis is established, disease risk in terms of thrombosis, fibrotic/leukemic
transformation and survival are assessed (Table 1). Thrombosis, including arterial and venous
events following diagnosis occur in over a third of patients, incidence of fibrotic
transformation is estimated at 16%, and there is a small (<5%) but definitive risk of leukemic
transformation. Additional, non- life threatening symptoms include pruritus and
microvascular symptoms. Survival in PV patients is inferior to age and sex matched control
population. The goals of therapy are mainly to minimize thrombosis risk which is achieved by
instituting a risk-adapted approach (Table 1 and Figure 1).
Aspirin 81 mg daily and phlebotomy to target hematocrit < 45% are the cornerstone of
therapy. Thrombosis history mandates cytoreductive agents. Hydroxyurea is the first line
agent of choice at a dose of 500 mg twice daily, and in patients that are refractory or intolerant
to hydroxyurea we prefer pegylated interferon 2α as the second line agent of choice.
Pegylated interferon is initiated at a dose of 45 mcg weekly and up-titrated based on
tolerability and response. Ropegylated interferon (Ropeg) is approved by the EMA for PV but
is not yet available in the USA. Data from the 5 year follow up of the Conti-PV study confirms
durable responses, including hematological and symptom responses. Importantly, molecular
responses were noted in over two third of patients. Moreover, toxicities were comparable to
other therapies mainly hydroxyurea. Recently, Ropeg was also studied in 100 patients with
low-risk PV, in which ropeg demonstrated superior hematocrit control, along with spleen and
symptom response compared to phlebotomy alone. Busulfan is an option for elderly patients
but one needs to be mindful of drug associated myelosuppression. Ruxolitinib is FDA-approved
for hydroxyurea refractory PV, providing hematocrit, spleen and symptom control,
and is considered in situations when a patient is refractory or intolerant to the above agents.
In order to eliminate phlebotomy needs in PV, a hepcidin-mimetic (PTG-300) is under
investigation; in a small cohort of 18 patients, phlebotomy needs were eliminated, iron levels
normalized, consequently symptoms were improved. Injection site reactions and
gastrointestinal toxicities were noted. Based on preliminary evidence, my recommendation
would be to pursue cytoreductive therapy instead. Other novel agents in trials are idasanutlin
(MDM2 antagonist) and ginivostat (histone deacetylate inhibitor).
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES