TY - JOUR
T1 - SOHO State of the Art Updates and Next Questions
T2 - Identifying and Treating “Progression” in Myelofibrosis
AU - Bose, Prithviraj
AU - Verstovsek, Srdan
N1 - Publisher Copyright:
© 2021
PY - 2021/10
Y1 - 2021/10
N2 - Over the last decade, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has become widely established as the cornerstone of pharmacologic therapy for most patients with myelofibrosis (MF), providing dramatic and durable benefits in terms of splenomegaly and symptoms, and prolonging survival. Ruxolitinib does not address all aspects of the disease, however; notably cytopenias, and its ability to modify the underlying biology of the disease remains in question. Furthermore, patients eventually lose response to ruxolitinib. Multiple groups have reported the median overall survival of MF patients after ruxolitinib discontinuation to be 13 to 14 months. While consensus criteria only recognize splenic and blast progression as “progressive disease” in patients with MF, disease progression can occur in a variety of ways. Besides increasing splenomegaly and progression to accelerated phase/leukemic transformation, patients may develop worsening disease-related symptoms, cytopenias, progressive leukocytosis, extramedullary hematopoiesis, etc. As in the frontline setting, treatment needs to be tailored to the clinical needs of the patient. Current treatment options for patients with MF who fail ruxolitinib remain unsatisfactory, and this continues to represent an area of major unmet medical need. The regulatory approval of fedratinib has introduced an important option in the postruxolitinib setting. Fortunately, a plethora of novel agents, both new JAK inhibitors and drugs from other classes, eg, bromodomain and extraterminal (BET), murine double minute 2 (MDM2) and telomerase inhibitors, activin receptor ligand traps, BH3-mimetics and more, are poised to greatly expand the therapeutic armamentarium for patients with MF if successful in pivotal trials.
AB - Over the last decade, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has become widely established as the cornerstone of pharmacologic therapy for most patients with myelofibrosis (MF), providing dramatic and durable benefits in terms of splenomegaly and symptoms, and prolonging survival. Ruxolitinib does not address all aspects of the disease, however; notably cytopenias, and its ability to modify the underlying biology of the disease remains in question. Furthermore, patients eventually lose response to ruxolitinib. Multiple groups have reported the median overall survival of MF patients after ruxolitinib discontinuation to be 13 to 14 months. While consensus criteria only recognize splenic and blast progression as “progressive disease” in patients with MF, disease progression can occur in a variety of ways. Besides increasing splenomegaly and progression to accelerated phase/leukemic transformation, patients may develop worsening disease-related symptoms, cytopenias, progressive leukocytosis, extramedullary hematopoiesis, etc. As in the frontline setting, treatment needs to be tailored to the clinical needs of the patient. Current treatment options for patients with MF who fail ruxolitinib remain unsatisfactory, and this continues to represent an area of major unmet medical need. The regulatory approval of fedratinib has introduced an important option in the postruxolitinib setting. Fortunately, a plethora of novel agents, both new JAK inhibitors and drugs from other classes, eg, bromodomain and extraterminal (BET), murine double minute 2 (MDM2) and telomerase inhibitors, activin receptor ligand traps, BH3-mimetics and more, are poised to greatly expand the therapeutic armamentarium for patients with MF if successful in pivotal trials.
KW - Disease progression
KW - Fedratinib
KW - Imetelstat
KW - JAK inhibitors
KW - KRT-232
KW - Luspatercept
KW - Momelotinib
KW - Pacritinib
KW - Pelabresib
KW - Ruxolitinib failure
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UR - http://www.scopus.com/inward/citedby.url?scp=85110313379&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2021.06.008
DO - 10.1016/j.clml.2021.06.008
M3 - Review article
C2 - 34272171
AN - SCOPUS:85110313379
SN - 2152-2650
VL - 21
SP - 641
EP - 649
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 10
ER -