CML

Question 1

CML risk factor

Answer 1

Ionizing radiation

Question 2

CML symptoms

Answer 2

Splenomegaly: >50% present → abdominal pain, early satiety
Anorexia, bone pain, purpura, unexplained weight loss, fatigue

Question 3

CML lab findings

Answer 3

Leukocytosis: WBX >25 x 10^9/L
Thrombocytosis on CBC with diff
Ph+ positive

Question 4

Ultimate goal of CML therapy

Answer 4

Get patient to chronic phase and stay there, prevent progression to AP or BP

Question 5

CP goal of CML

Answer 5

delay progression to AP/BP, eradicate Philadelphia chromosome

Question 6

AP goal of CML

Answer 6

control WBC count, bring back to CP and avoid progression to BP

Question 7

BP goal of CML

Answer 7

Survive induction, bridge to allogeneic stem cell transplant

Question 8

CML treatment

Answer 8

TKIs!

Question 9

Initial selection of TKIs in CML

Answer 9

Low-risk score: imatinib or any second generation TKI
Intermediate-high risk score: any second generation TKI

Question 10

AP/CP goal

Answer 10

Return patient to chronic phase

Question 11

Accelerated phase treatment

Answer 11

Second generation TKI preferred
Omacetaxine can be considered in some cases d/t resistance or intolerance to ≥2 TKIs
Consider allogeneic transplant

Question 12

Blast crisis treatment

Answer 12

TKI +/- chemo followed by allogeneic HSCT
Chemo chosen is based on subtype of disease
AML or ALL-based induction regimens

Question 13

Side effects common in ALL TKIs

Answer 13

Myelosuppression
Transaminitis
Electrolyte changes

Question 14

1st generation TKI

Answer 14

imatinib

Question 15

AEs of imatinib (besides the ones common in all TKIs)

Answer 15

edema/fluid retention
Myalgias
Hypophosphatemia
N/V/D

Question 16

Imatinib dose adjustments

Answer 16

Need to adjust in renal and hepatic impairment

Question 17

Imatinib DDIs

Answer 17

3A4 substrate and inhibitor

Question 18

Imatinib MoA

Answer 18

Selective inhibitor of BCR-ABL TKI

Inhibits c-KIT and platelet-derived growth factor receptor (PDGFR)

Question 19

2nd generation TKIs

Answer 19

Dasatinib, nilotinib

Question 20

Dasatinib MoA

Answer 20

Dual inhibitor of BCR-ABL and Src family of kinases; also inhibits c-KIT and PDGFR

Question 21

Dasatinib AEs (besides the common class effects)

Answer 21

Pleural/pericardial effusions
Bleeding risk
Pulmonary arterial HTN

Question 22

Dasatinib is the _____ of treatment

Answer 22

Mainstay!

Question 23

Dasatinib DDIs

Answer 23

3A4 substrate

Question 24

Dasatinib absorption requirements

Answer 24

Needs an acidic environment, so no PPIs or H2RAs

Question 25

Nilotinib AEs (besides the class effects)

Answer 25

Elevated pancreatic enzymes Indirect hyperbilirubinemia QTc prolongation- BBW CV events

Question 26

Nilotinib metabolism

Answer 26

3A4 substrate and inhibitor; also 2C8, 2C9, 2D6

Question 27

Nilotinib dose adjustment

Answer 27

Adjust in hepatic impairment

Question 28

Nilotinib monitoring

Answer 28

Lipid panel

Question 29

Nilotinib administration

Answer 29

Empty stomach 2 hours before or 1 hour after eating

Question 30

3rd generation TKIs

Answer 30

Bosutinib, ponatinib

Question 31

Bosutinib MoA

Answer 31

Dual activity against BCR-ABL, Src, Lyn, and Hck kinases Has activity against many BCR-ABL mutations that are resistant to imatinib, dasatinib, and nilotinib (except T315I and V299L)

Question 32

Bosutinib AEs (besides class effects)

Answer 32

N/V/D, rash, HA

Question 33

Bosutinib indication

Answer 33

Approved for newly diagnosed CML upfront, advanced disease including resistance/intolerance to prior therapy

Question 34

Bosutinib metabolism

Answer 34

3A4 substrate

Question 35

Bosutinib dose adjustment

Answer 35

Adjust in hepatic impairment

Question 36

Ponatinib MoA

Answer 36

Targets VEGFR, PDGFR, Src, FGFR, FLT3, RTK, TIE2 Active against ALL BCR-ABL point mutations, including T315I

Question 37

Ponatinib AEs

Answer 37

BBW for vascular occlusion, HF, hepatoxicity Elevated pancreatic enzymes HTN Skin toxicity Thrombotic events

Question 38

Ponatinib indication

Answer 38

Approved for patients with T315I mutation and for those whom no other TKI therapy is indicated

Question 39

Ponatinib metabolism

Answer 39

3A4 substrate

Question 40

Ponatinib dose adjustment

Answer 40

Adjust in hepatic impairment

Question 41

Asciminib drug class

Answer 41

STAMP inhibitor

Question 42

Asciminib MoA

Answer 42

Targets ABL1 Myristoyl pocket Allosteric inhibitor

Question 43

Asciminib indication

Answer 43

Patients who have previously received 2+ TKIs or those with T315I mutation

Question 44

Asciminib administration

Answer 44

Empty stomach 2 hours before or 1 hour after eating

Question 45

Omacetaxine mepesuccinate MoA

Answer 45

Reversible inhibitor of protein synthesis

Question 46

Omacetaxine mepesuccinate indication

Answer 46

Patients with resistance and/or intolerance to 2 or more TKIs

Question 47

Omacetaxine mepesuccinate AEs

Answer 47

Myelosuppression Nausea Diarrhea Fever