CML NCCN v 2.2023 Flashcards
Early molecular response (EMR; ≤10% BCR::ABL1 IS at 3 and 6 months) after first-line TKI therapy has emerged as an effective prognosticator of
favorable long-term PFS and OS
MS-10
True or False
if BCR::ABL1 transcript level is minimally above the 10% cutoff (eg, 11%–15% at 3 months), it is reasonable to reassess at 6 months before considering major changes to the treatment strategy
True
MS-10
Achievement of CCyR or ≤1% BCR::ABL1 IS within 12 months after first-line TKI therapy is an established prognostic indicator of
long-term survival
MS-10
The most important goals of TKI therapy are to
1) prevent disease progression to AP-CML or BP-CML
2) to achieve either
``MR2.0 (≤1% BCR::ABL1 IS, which corresponds to CCyR)
or
MMR (≤0.1% BCR::ABL1 IS) within 12 months after first-line TKI therapy.
MS-11
True/False
achievement of EMR after first-line TKI therapy is an effective prognosticator of favorable long-term PFS
TRUE
Achievement of >0.1%–1% BCR::ABL1 IS (≤1% BCR::ABL1 IS, which correlates with CCyR) is considered the optimal response milestone at 12 months if the goal of therapy is
long-term survival
MS-11
Achievement of MMR (≤0.1% BCR::ABL1 IS) at 12 months should be considered as the optimal response milestone if the treatment goal is
TFR
Failure to achieve ≤10% BCR::ABL1 IS at 3 months or ≤1% BCR::ABL1 IS at 12 months is associated with a
higher risk for disease progression.
MS-12
Patients with >10% BCR::ABL1 IS at 6 and 12 months are considered to have
TKI-resistant disease.
MS-12
True/False
In patients with >0.1%–1% BCR::ABL1 IS at 12 months, shared decision-making is recommended depending on the goal of therapy in individual patients (longer-term survival vs. TFR)
TRUE
are active against most of the resistant BCR::ABL1 kinase domain mutants including T315I
ponatinib and asciminib
Ponatinib was initially approved as a treatment option for patients with a T315I mutation and/or for patients for whom no other TKI is indicated based on the results of the ____
PACE trial
MS-12
The high-dose intensity of ponatinib was associated with increased risk of
arterial occlusive events (AOE)
(in 31% of the patients)
MS-13
Based on the results of the _____ trial, the FDA has approved a response-adjusted dosing regimen for ponatinib [starting dose of 45 mg once daily with a reduction to 15 mg upon achievement of BCR::ABL1 (IS) ≤1%] for patients with CP-CML with resistance or intolerance to at least two prior kinase inhibitors.
OPTIC
MS-13
The recommended initial dose of asciminib is (___) or (___) in patients without a T315I mutation and (___) for patients with a T315I mutation.
80 mg once daily or 40 mg twice daily
200 mg twice daily
MS-13
True or False
EMR (≤10% BCR::ABL1 IS at 3 and 6 months) after second-line TKI therapy with dasatinib or nilotinib has also been reported to be a prognosticator of OS and PFS
True
MS-14
True/False
All TKIs are metabolized in the liver by cytochrome P450 (CYP) enzymes
TRUE
identified as the only independent predictor for achieving complete molecular response (CMR) on standard-dose imatinib
Adherence to imatinib therapy
MS-14
identified as the most important factor contributing to cytogenetic relapse and imatinib failure
Poor adherence to imatinib therapy
reported as the most powerful predictor of response to imatinib
Pretreatment levels of organic cation transporter 1 (OCT1)
MS-15
T/F
cellular uptake of dasatinib or nilotinib seems to be dependent of OCT1 expression
FALSE
cellular uptake of dasatinib or nilotinib seems to be** independent** of OCT1 expression
low OCT1 expression better outcome w/ dasa or nilo than vs ima
MS-15
(4) mutants are most commonly associated with disease progression and relapse
- E255K/V,
- F359C/V,
- Y253H
- T315I
Ponatinib is active in those mutations
MS-15
confers complete resistance to imatinib, dasatinib, nilotinib, and bosutinib
T315I
Contraindicated Mutations for Dasatinib
T315I/A,
F317L/V/I/C, or
V299L
CML-5
Contraindicated Mutations for Nilotinib
T315I,
Y253H,
E255K/V, or
F359V/C/I
Contraindicated Mutations for Bosutinib
T315I,
V299L,
G250E, or
F317L
Common contraindicated mutations for Dasa and Bosu
T315I, V299L, F317L
Post transplant, patients who are in CCyR (qPCR-negative) should undergo regular qPCR monitoring every…
3 months for 2 years, then every 3–6 months thereafter
MS-24
True/False
Pre-existing mutations in the BCR::ABL1 kinase domain, are no longer detectable in the majority of patients who relapse after allogeneic HCT
FALSE
Pre-existing mutations in the BCR::ABL1 kinase domain, frequently associated with resistance to TKIs, are detectable in the majority of patients who relapse after allogeneic HCT
mutational analysis is needed prior to selection of TKI
MS-23
Allogeneic HCT is an appropriate treatment option for the very rare patients presenting with
1) BP-CML at diagnosis,
2) disease that is resistant to TKIs,
3) progression to AP-CML or BP-CML while on TKI therapy,
4) CML that is resistant and/or intolerant to all TKIs
MS-22
T/F
prior TKI therapy can compromise the outcome following allogeneic HCT or increase transplant-related toxicity
False
prior TKI therapy does not compromise the outcome following allogeneic HCT or increase transplant-related toxicity
MS-22
factors that predict the risk of recurrence after discontinuation of TKI therapy
- a higher Sokal risk score,
- female gender,
- lower natural killer cell counts,
- suboptimal response or resistance to imatinib,
- duration of TKI therapy, and
- DMR prior to TKI discontinuation
MS-18
Indications for BCR::ABL1 kinase domain mutational analysis
1) for patients who do not achieve response milestones,
2) for any sign of loss of response (hematologic or cytogenetic relapse), and
3) if there is a 1-log increase in BCR::ABL1 level with loss of MMR
MS-16
Mutations in _ gene are most commonly described secondary alterations in patients with CP-CML and have been identified as an independent predictor of inferior EFS rates.
ASXL1
MS-16
allows for the detection of low-level BCR::ABL1 kinase domain mutations as well as resistance mutations in genes other than BCR::ABL1 that may confer resistance to TKIs or portend disease progression.
Next generation sequencing (NGS)
MS-16
