Monitoring
Treatment Response Assessment
Complete Hematologic Response
- Normalization of the peripheral blood counts with <10 × 10⁹/L of leukocytes
- <450 × 10⁹/L platelet count
- <5% basophils
- Immature granulocytes (eg myelocytes, promyelocytes, blasts in peripheral blood) absent
- Spleen is non-palpable and no signs and symptoms of the disease are present
Cytogenetic Response
- No Ph-positive metaphases: CCyR
- 0-35% Ph-positive metaphases: Major cytogenetic response (MCyR)
- 1-35% Ph-positive metaphases: PCyR
- >35-65% Ph-positive metaphases: Minor cytogenetic response
- 36-95% Ph-positive metaphases: Minimal cytogenetic response
- >95% Ph-positive metaphases: Cytogenetic response absent
Molecular Response
- Early molecular response (EMR): BCR::ABL1 transcripts ≤10% by qPCR (IS) at 3 and 6 months
- MMR: BCR::ABL1 transcripts ≤0.1% by qPCR (IS) or a reduction of ≥3 log in the BCR::ABL1 mRNA, if qPCR (IS) is unavailable
- DMR: BCR::ABL1 values of ≤0.01% IS and is described as various BCR::ABL1 cutoff values (ie MR4.0 ≤0.01% IS, MR4.5 ≤0.0032% IS)
Relapse
- Any signs of loss of hematologic response or CCyR (BCR::ABL1 ≤1%) or its molecular response correlate (MR2.0: BCR::ABL1 [IS] ≤1%) (increase in BCR::ABL1 transcripts to >1%)
- 1-log increase in the BCR::ABL1 transcripts level with loss of MMR
Monitoring Response to TKI Therapy
Hematologic
Tests
CBC is recommended every 1 to 2 weeks within the first 1 to 2 months of
treatment or until blood counts stabilize and thereafter as indicated based on
the persistence of cytopenias.
Bone Marrow Cytogenetics
Bone marrow cytogenetics is used to establish the phase of CML and performed at diagnosis. It may
be used after the initiation of a TKI therapy at 3 and 6 months, and if qPCR
(IS) is not available. It may also be done if there is a failure to reach
response milestones, signs of loss of hematologic response, or signs of CCyR or
its molecular correlate (increase in BCR::ABL1 transcript levels to >1%).
qPCR
qPCR is the preferred method for monitoring response to TKI therapy. It is performed at diagnosis. It
is recommended to be performed every 3 months after the initiation of therapy,
including in patients who have met response milestones. It may be repeated
every 3 months for 2 years and every 3 to 6 months thereafter, if the CCyR has
been achieved. It should be repeated in 1 to 3 months if the BCR::ABL1
transcript levels with MMR have increased by 1-log.
BCR::ABL Kinase Domain Mutation Analysis
Recommendations
for CP:
- Failure to reach response milestones
- There are signs of loss of hematologic response or CCyR or its molecular response correlate (increase in BCR::ABL1 transcripts >1%)
- There is lack of MMR and the BCR::ABL1 transcript levels have increased by 1-log
- Consider myeloid mutation panel to identify BCR::ABL1-independent resistance mutations in patients without BCR::ABL1 kinase domain mutation
Recommendations
for AP or BP: To monitor if the disease has progressed to AP or BP.
Follow-up
Factors
affecting the patient’s compliance include the length of time from diagnosis to
treatment and history of Imatinib treatment,
age, dose of TKI, living along, and male sex.
Three
Months Follow-up Therapy
For
patients with BCR::ABL1 transcripts ≤10% by qPCR (IS), the patient is
advised to continue the same TKI with the same dose, and response is monitored
with qPCR; adverse effects are also monitored.
For
patients with BCR::ABL1 transcripts ≥10% by qPCR (IS):
- Evaluate the compliance of the patient and report for drug interactions
- Advise the patient to have mutational analysis
- Bone marrow cytogenetic analysis to assess MCyR at 3 months and CCyR at 12 months should be considered
- Advise the patient to enroll in a clinical trial
- Switch to an alternate TKI or continue the same TKI at the same dose for another 3 months; Imatinib is associated with slower molecular response
- May continue the same TKI other than Imatinib for another 3 months if with ≥50% reduction from baseline or >10% cutoff
- Evaluate the patient for allo-HCT
Six Months Follow-up Therapy
For
patients with BCR::ABL1 transcripts <10% by qPCR (IS), the patient is
advised to continue the same TKI, and response is monitored with qPCR; adverse
effects are also monitored.
For
patients with BCR::ABL1 transcripts >10% by qPCR (IS):
- Evaluate the compliance of the patient and report for drug interactions
- Advise the patient to have mutational analysis
- Advise the patient to enroll in a clinical trial
- Change therapy to other TKIs
- Evaluate the patient for allo-HCT
Twelve
Months Follow-up Therapy
For
patients with BCR::ABL1 transcripts ≤0.1% by qPCR (IS), the patient is
advised to continue the same TKI, and response is monitored with qPCR; adverse
effects are also monitored. One may also consider a trial of treatment-free
remission.
For patients with BCR::ABL1 transcripts ≤1% but >0.1% by
qPCR (IS):
- Advise to continue taking the same TKI if
treatment goal is optimal
- Optimal treatment goal focused on long term survival: >0.1-1%
- Optimal treatment goal focused on treatment-free survival: ≤0.1%
- If the optimal treatment goal is not achieved, shared decision-making with the patient on switching of treatment (Imatinib to a second generation TKI or allosteric TKI) and enrollment in a clinical trial should be considered
For patients with BCR::ABL1 transcripts ≤10% but is >1% by qPCR (IS):
- Evaluate compliance of the patient and report for drug interactions
- Consider the patient for mutational analysis
- Bone marrow cytogenetic analysis to assess MCyR at 3 months and CCyR at 12 months should be considered
- Consider switching to an alternate TKI or continue the same TKI if CCyR is achieved
- Evaluate the patient for allo-HCT
For patients with BCR::ABL1 transcripts >10% by qPCR (IS):
- Evaluate compliance of the patient and report for drug interactions
- Consider the patient for mutational analysis
- Switch to an alternate TKI (other than Imatinib) and evaluate the patient for allo-HCT
Chronic Myeloid Leukemia_Follow Up