Abstract
Introduction: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
| Original language | English |
|---|---|
| Pages (from-to) | 1597-1611 |
| Number of pages | 15 |
| Journal | Expert Opinion on Pharmacotherapy |
| Volume | 12 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jul 2011 |
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Keywords
- demethylating agents
- histone deacetylase inhibitors
- JAK2 inhibitors
- JAK2 V617F mutation
- mTOR inhibitors
- myelofibrosis
- myeloproliferative neoplasm
- response criteria
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
Cite this
Therapeutic approaches in myelofibrosis. / Barosi, Giovanni; Rosti, Vittorio; Vannucchi, Alessandro M.
In: Expert Opinion on Pharmacotherapy, Vol. 12, No. 10, 07.2011, p. 1597-1611.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Therapeutic approaches in myelofibrosis
AU - Barosi, Giovanni
AU - Rosti, Vittorio
AU - Vannucchi, Alessandro M.
PY - 2011/7
Y1 - 2011/7
N2 - Introduction: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
AB - Introduction: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
KW - demethylating agents
KW - histone deacetylase inhibitors
KW - JAK2 inhibitors
KW - JAK2 V617F mutation
KW - mTOR inhibitors
KW - myelofibrosis
KW - myeloproliferative neoplasm
KW - response criteria
UR - http://www.scopus.com/inward/record.url?scp=79958697713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958697713&partnerID=8YFLogxK
U2 - 10.1517/14656566.2011.568939
DO - 10.1517/14656566.2011.568939
M3 - Article
C2 - 21457082
AN - SCOPUS:79958697713
VL - 12
SP - 1597
EP - 1611
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
IS - 10
ER -