CML NCCN v 2.2023

Question 1

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

Answer 1

favorable long-term PFS and OS

MS-10

Question 2

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

Answer 2

True

MS-10

Question 3

Achievement of CCyR or ≤1% BCR::ABL1 IS within 12 months after first-line TKI therapy is an established prognostic indicator of

Answer 3

long-term survival

MS-10

Question 4

The most important goals of TKI therapy are to

Answer 4

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

Question 5

True/False

achievement of EMR after first-line TKI therapy is an effective prognosticator of favorable long-term PFS

Answer 5

TRUE

Question 6

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

Answer 6

long-term survival

MS-11

Question 7

Achievement of MMR (≤0.1% BCR::ABL1 IS) at 12 months should be considered as the optimal response milestone if the treatment goal is

Answer 7

TFR

Question 8

Failure to achieve ≤10% BCR::ABL1 IS at 3 months or ≤1% BCR::ABL1 IS at 12 months is associated with a

Answer 8

higher risk for disease progression.

MS-12

Question 9

Patients with >10% BCR::ABL1 IS at 6 and 12 months are considered to have

Answer 9

TKI-resistant disease.

MS-12

Question 10

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)

Answer 10

TRUE

Question 11

are active against most of the resistant BCR::ABL1 kinase domain mutants including T315I

Answer 11

ponatinib and asciminib

Question 12

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 ____

Answer 12

PACE trial

MS-12

Question 13

The high-dose intensity of ponatinib was associated with increased risk of

Answer 13

arterial occlusive events (AOE)

(in 31% of the patients)

MS-13

Question 14

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.

Answer 14

OPTIC

MS-13

Question 15

The recommended initial dose of asciminib is (___) or (___) in patients without a T315I mutation and (___) for patients with a T315I mutation.

Answer 15

80 mg once daily or 40 mg twice daily

200 mg twice daily

MS-13

Question 16

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

Answer 16

True

MS-14

Question 17

True/False

All TKIs are metabolized in the liver by cytochrome P450 (CYP) enzymes

Answer 17

TRUE

Question 18

identified as the only independent predictor for achieving complete molecular response (CMR) on standard-dose imatinib

Answer 18

Adherence to imatinib therapy

MS-14

Question 19

identified as the most important factor contributing to cytogenetic relapse and imatinib failure

Answer 19

Poor adherence to imatinib therapy

Question 20

reported as the most powerful predictor of response to imatinib

Answer 20

Pretreatment levels of organic cation transporter 1 (OCT1)

MS-15

Question 21

T/F

cellular uptake of dasatinib or nilotinib seems to be dependent of OCT1 expression

Answer 21

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

Question 22

(4) mutants are most commonly associated with disease progression and relapse

Answer 22

• E255K/V,
• F359C/V,
• Y253H
• T315I

Ponatinib is active in those mutations

MS-15

Question 23

confers complete resistance to imatinib, dasatinib, nilotinib, and bosutinib

Answer 23

T315I

Question 24

Contraindicated Mutations for Dasatinib

Answer 24

T315I/A,
F317L/V/I/C, or
V299L

CML-5

Question 25

Contraindicated Mutations for Nilotinib

Answer 25

T315I,
Y253H,
E255K/V, or
F359V/C/I

Question 26

Contraindicated Mutations for Bosutinib

Answer 26

T315I,
V299L,
G250E, or
F317L

Question 27

Common contraindicated mutations for Dasa and Bosu

Answer 27

T315I, V299L, F317L

Question 28

Post transplant, patients who are in CCyR (qPCR-negative) should undergo regular qPCR monitoring every…

Answer 28

3 months for 2 years, then every 3–6 months thereafter

MS-24

Question 29

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

Answer 29

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

Question 30

Allogeneic HCT is an appropriate treatment option for the very rare patients presenting with

Answer 30

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

Question 31

T/F

prior TKI therapy can compromise the outcome following allogeneic HCT or increase transplant-related toxicity

Answer 31

False

prior TKI therapy does not compromise the outcome following allogeneic HCT or increase transplant-related toxicity

MS-22

Question 32

factors that predict the risk of recurrence after discontinuation of TKI therapy

Answer 32

• 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

Question 33

Indications for BCR::ABL1 kinase domain mutational analysis

Answer 33

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

Question 34

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.

Answer 34

ASXL1

MS-16

Question 35

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.

Answer 35

Next generation sequencing (NGS)

MS-16