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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Myeloproliferative Neoplasms (MPNs)
- Natural history of MPNs
- MPN driver mutations
- What to look for in the bone marrow of MPNs
- Major differences in classification of classical MPNs
- Overview of risk stratification
- Patients with post PV and post ET MF
- Assessing MF burden
- Evolution of MPN symptom assessment tools
- Classic signs and symptoms of MPNs
- Case presentation: primary MF
- 2017 WHO diagnostic criteria for prePMF
- 2017 WHO diagnostic criteria for overt PMF
- MF grading
- IWG-MRT diagnostic criteria for post-PV MF
- IWG-MRT diagnostic criteria for post-ET MF
- Risk stratification for patients with PMF
- Case: MF DIPSS
- Prognostic significance of mutations in MPN
- MIPSS-70 risk model
- Risk stratification for patients with PMF
- MIPSS-70: overall survival
- Case: MF MIPSS-70
- Risk stratification for patients with PMF
- Risk stratification: post-PV and post-ET MF
- Management of myelofibrosis 2022
- JAK inhibitor landscape 2022
- Case 1: intermediate-1 myelofibrosis (1)
- Case 1: intermediate-1 myelofibrosis (2)
- Case 1: intermediate-1 myelofibrosis (follow-up)
- Ruxolitinib phase III trials (COMFORT I & II)
- COMFORT I: symptom response
- Ruxolitinib efficacy by titrated dose: COMFORT-I
- Fedratinib (1)
- Fedratinib (2)
- JAKARTA-1: endpoints
- Using fedratinib (FEDR) in MF front line
- Pacritinib
- Proliferative vs. cytopenic MF
- Pacritinib: a selective inhibitor of JAK2 and IRAK1
- Pacritinib: phase 3 myelofibrosis studies
- PERSIST-2 ≥35% spleen volume reduction (SVR)
- PAC safety profile: predictable and manageable
- Now-approved pacritinib (Vonjo)
- Momelotinib (MMB): seeking approval
- Pivotal phase 3: ‘MOMENTUM’ trial overview
- MMB showed strong activity across key endpoints
- Novel agents developed in MPN, particularly MF
- Mechanism of potential disease modification in MF
- LSD1 inhibition: strong therapeutic rationale in MPN
- ACE-536-MF-001 (luspatercept) study design
- Selected additional single-agent trials in MF
- Selected JAKi-based rational combinations
- Ongoing or planned phase 3 studies in MF
- Takeaway 1
- Results: overall survival and overview
- Pooled overall survival analysis
- Results: OS ~ ruxolitinib
- Survival after ruxolitinib discontinuation
- SIMPLIFY-1: JAKi-naïve patients
- SIMPLIFY-2: prior-JAKi treated patients
- IMbark phase 2 imetelstat data: survival
- Potential OS improvement with 9.4 mg/kg imetelstat
- Questions? MF and survival
- Takeaway 2
- Comparison for 1L MF therapy
- Treatment for higher-risk MF
- Management of MF-associated anemia
- Step 1 for MF management: optimize JAK inhibition
- Strategies for non-JAKi MOA in MF
- What is precise and personalized cancer care?
- Acknowledgements
Topics Covered
- Myelofibrosis (MF)
- Myeloproliferative Neoplasms (MPNs)
- Polycythemia Vera (PV)
- Essential Thrombocytopenia (ET)
- MPN driver mutations
- Risk stratification for myelofibrosis
- MPN symptom assessment tools
- WHO diagnostic criteria for myelofibrosis
- Ruxolitinib
- Fedratinib
- Pacritinib
- Momelotinib
Talk Citation
Mesa, R.A. (2023, March 30). Myelofibrosis [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/OKBI6727.Export Citation (RIS)
Publication History
Financial Disclosures
- Consultant (Honoraria) over past 3 years: Novartis, Sierra Oncology, Genentech, Sierra, Blueprint, Geron, Telios, CTI, Incyte, BMS, Abbvie, GSK Research Support: Incyte, Sierra, CTI, BMS, Abbvie, Genentech, Blueprint, Morphosys.
A selection of talks on Oncology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Ruben Mesa,
and I´m the Executive Director
of the Mays Cancer Center
at UT Health San Antonio.
I'm delighted today
to present this
update on myelofibrosis:
diagnosis,
pathogenesis, treatment, and
issues with the survivorship
of these patients.
0:22
Here are my disclosures.
0:26
The myeloproliferative
neoplasms (MPNs) are a group of
chronic leukemias that
include myelofibrosis (MF),
polycythemia vera (PV), and
essential thrombocytopenia (ET).
They're heterogeneous and
they impact the
hematopoietic system.
Roughly in the United States,
we estimate about
350,000 patients,
with myelofibrosis being
the least prevalent.
The presenting symptoms can
be somewhat nonspecific,
often making the
diagnosis challenging.
0:58
The natural history of the MPNs
begins with earlier disease
and earlier disease
polycythemia vera,
essential thrombocytopenia,
and what we call
early myelofibrosis, or is now
termed pre-fibrotic myelofibrosis.
In this phase of these diseases,
the time question
can be very latent.
There can be risky
vascular events.
There can be symptoms frequently
that can be associated
with high counts and
difficulties with circulation.
Now, over time,
these diseases can
progress to myelofibrosis
and this progression is
an important transition.
We normally feel that patients
with ET / PV and
early myelofibrosis
do not have a dramatically
different life expectancy
than age-match controls,
although there certainly
are exceptions
in patients with
PV and early MF.
Those with overt MF
have a much more
challenging phenotype
of the disease.
They have progressive
constitutional symptoms.
They may have
cytopenias that can
have significant enlargement
of the spleen or liver.
They may transform
into acute leukemia,
and the disease can
be life-threatening.
Roughly the life expectancy
in this phase of
the disease is three
to five years.
However, this can be
quite heterogeneous.
There are some very
long-lived individuals.
Additionally, many
of the therapies
which are in development
may have an impact that may
help to prolong their survival.