Content on this page:
Content:
Monitoring
Treatment
Response Monitoring
MPN-SAF
TSS is used as a monitoring tool for treatment response. Symptom response
requires a reduction of ≥50% in the MPN-SAF TSS. A <50% reduction is
clinically significant and justifies continued use of Ruxolitinib. A change in
symptom status may be a sign of disease progression and should prompt an evaluation
of treatment efficacy and/or disease status. The assessment of treatment
response involves performing CBC to assess normalization of blood counts,
monitoring symptom status using MPN-SAF TSS, and monitoring spleen size by imaging
or palpation.
Monitoring
response (anemia response, spleen response, and symptom response) is
recommended every 3 to 6 months during the course of therapy. Continuation of
Ruxolitinib or Fedratinib is recommended for patients with <50% symptom
response at the discretion of the physician. Ruxolitinib should be discontinued
if there is no response or improvement of symptoms after 6 months.
Bone
marrow aspirate and biopsy should be performed when increased symptoms or signs
of progression are present.
Molecular
testing with multigene NGS panel may be performed in patients with higher-risk myelofibrosis
to assess for high molecular risk mutations which are associated with disease
progression. ASXL1, TET2, TP53, SRSF2, IDH1, and IDH2 gene
mutations and other chromosomal abnormalities (in chromosome 1q and 9p) are
associated with transformation to acute myeloid leukemia.
Disease
progression of myelofibrosis to accelerated phase (MF-AP) is characterized by
the presence of <50 x 109/L platelets, chromosome 17
abnormalities, and ≥10% (10-19%) blasts in bone marrow or peripheral blood. The
disease progression of myelofibrosis in the blast phase (MF-BP) is synonymous
to acute myeloid leukemia and is characterized by the presence of ≥20% myeloid
blasts in peripheral blood or bone marrow.
2013 IWG-MRT and ELN Response Criteria for Myelofibrosis
Response Categories |
Required Criteria (response should last ≥12 weeks) | |
Complete response | Bone marrow:
Peripheral blood:
|
Clinical:
|
Partial response |
Peripheral blood:
Bone marrow:
Peripheral blood:
|
Clinical:
|
Progressive disease |
|
|
Clinical improvement (CI) |
Achievement of anemia, spleen, or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia | |
Relapse |
|
|
Anemia response |
|
|
Spleen response |
|
|
Symptom response |
≥50% reduction in the MPN-SAF TSS | |
Stable disease |
Belonging to none of the above-listed response categories | |
Recommendations for the Assessment of Treatment-induced Cytogenetic and Molecular Changes | ||
Cytogenetic remission | Cytogenic response evaluation should include ≥10
metaphases and confirmed using repeat testing within 6 months
Complete remission: Clearance of a pre-existing abnormality Partial remission: ≥50% reduction in abnormal metaphases (for patients with ≥10 abnormal metaphases at baseline) |
|
Molecular remission |
Peripheral blood analysis should be included in the evaluation
of molecular response and confirmed using repeat testing within six months
Complete remission: Clearance of a pre-existing abnormality Partial remission: ≥50% decrease in allele burden (for patients with ≥20% mutant allele burden at baseline) |
|
Cytogenetic/molecular remission |
Re-emergence of a pre-existing cytogenetic or molecular abnormality that
is confirmed by repeat testing |
MF: Myelofibrosis; ULN: Upper Limit Normal
Management of Disease
Progression
The treatment options for patients with disease
progression are based on transplant eligibility. Workup includes bone marrow
aspirate and biopsy with reticulin and trichome stain, bone marrow cytogenetics
if the bone marrow is inaspirable, flow cytometry, and molecular testing for acute
myeloid leukemia-associated mutations.
Continuation of Ruxolitinib or Fedratinib to the
start of conditioning therapy is recommended to reduce splenomegaly and improve
other disease-related symptoms.
Transplant-eligible Patients
Reduction
of blast counts or disease control may be achieved with hypomethylating agents
(Azacitidine or Decitabine) or with intensive acute myeloid leukemia-type
induction chemotherapy followed by allogeneic hematopoietic stem cell
transplant. Enrollment in clinical trials may be another option.
Transplant-ineligible Patients
Treatment
with hypomethylating agents or low-intensity acute myeloid leukemia-type
induction chemotherapy or enrollment in clinical trials is recommended.
Prognosis
Prognostic Markers
The presence of triple-negative mutation status
(absence of JAK2, CALR, or MPL mutations) is associated with a worse
prognosis in patients with primary myelofibrosis.
The
presence of ASXL1, EZH2, SRSF2, TP53, IDH1, or IDH2 mutations are
high-molecular risk mutation and are associated with shorter overall survival and
leukemia-free survival in patients with primary myelofibrosis. ASXL1, EZH2, and
SRSF2 mutations are predictive of overall survival. ASXL1, SRSF2, and
IDH1 or IDH2 mutations are predictive of leukemic transformation.
The
presence of TET2 or TP53 mutations is associated with a worse
overall prognosis and an increased rate of leukemic transformation. The presence
of U2AF1 mutations is associated with poorer survival in patients with primary
myelofibrosis.