CML Flashcards
CML risk factor
Ionizing radiation
CML symptoms
Splenomegaly: >50% present → abdominal pain, early satiety
Anorexia, bone pain, purpura, unexplained weight loss, fatigue
CML lab findings
Leukocytosis: WBX >25 x 10^9/L
Thrombocytosis on CBC with diff
Ph+ positive
Ultimate goal of CML therapy
Get patient to chronic phase and stay there, prevent progression to AP or BP
CP goal of CML
delay progression to AP/BP, eradicate Philadelphia chromosome
AP goal of CML
control WBC count, bring back to CP and avoid progression to BP
BP goal of CML
Survive induction, bridge to allogeneic stem cell transplant
CML treatment
TKIs!
Initial selection of TKIs in CML
Low-risk score: imatinib or any second generation TKI
Intermediate-high risk score: any second generation TKI
AP/CP goal
Return patient to chronic phase
Accelerated phase treatment
Second generation TKI preferred
Omacetaxine can be considered in some cases d/t resistance or intolerance to ≥2 TKIs
Consider allogeneic transplant
Blast crisis treatment
TKI +/- chemo followed by allogeneic HSCT
Chemo chosen is based on subtype of disease
AML or ALL-based induction regimens
Side effects common in ALL TKIs
Myelosuppression
Transaminitis
Electrolyte changes
1st generation TKI
imatinib
AEs of imatinib (besides the ones common in all TKIs)
edema/fluid retention
Myalgias
Hypophosphatemia
N/V/D
Imatinib dose adjustments
Need to adjust in renal and hepatic impairment
Imatinib DDIs
3A4 substrate and inhibitor
Imatinib MoA
Selective inhibitor of BCR-ABL TKI
Inhibits c-KIT and platelet-derived growth factor receptor (PDGFR)
2nd generation TKIs
Dasatinib, nilotinib
Dasatinib MoA
Dual inhibitor of BCR-ABL and Src family of kinases; also inhibits c-KIT and PDGFR
Dasatinib AEs (besides the common class effects)
Pleural/pericardial effusions
Bleeding risk
Pulmonary arterial HTN
Dasatinib is the _____ of treatment
Mainstay!
Dasatinib DDIs
3A4 substrate
Dasatinib absorption requirements
Needs an acidic environment, so no PPIs or H2RAs
Nilotinib AEs (besides the class effects)
Elevated pancreatic enzymes
Indirect hyperbilirubinemia
QTc prolongation- BBW
CV events
Nilotinib metabolism
3A4 substrate and inhibitor; also 2C8, 2C9, 2D6
Nilotinib dose adjustment
Adjust in hepatic impairment
Nilotinib monitoring
Lipid panel
Nilotinib administration
Empty stomach 2 hours before or 1 hour after eating
3rd generation TKIs
Bosutinib, ponatinib
Bosutinib MoA
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)
Bosutinib AEs (besides class effects)
N/V/D, rash, HA
Bosutinib indication
Approved for newly diagnosed CML upfront, advanced disease including resistance/intolerance to prior therapy
Bosutinib metabolism
3A4 substrate
Bosutinib dose adjustment
Adjust in hepatic impairment
Ponatinib MoA
Targets VEGFR, PDGFR, Src, FGFR, FLT3, RTK, TIE2
Active against ALL BCR-ABL point mutations, including T315I
Ponatinib AEs
BBW for vascular occlusion, HF, hepatoxicity
Elevated pancreatic enzymes
HTN
Skin toxicity
Thrombotic events
Ponatinib indication
Approved for patients with T315I mutation and for those whom no other TKI therapy is indicated
Ponatinib metabolism
3A4 substrate
Ponatinib dose adjustment
Adjust in hepatic impairment
Asciminib drug class
STAMP inhibitor
Asciminib MoA
Targets ABL1 Myristoyl pocket
Allosteric inhibitor
Asciminib indication
Patients who have previously received 2+ TKIs or those with T315I mutation
Asciminib administration
Empty stomach 2 hours before or 1 hour after eating
Omacetaxine mepesuccinate MoA
Reversible inhibitor of protein synthesis
Omacetaxine mepesuccinate indication
Patients with resistance and/or intolerance to 2 or more TKIs
Omacetaxine mepesuccinate AEs
Myelosuppression
Nausea
Diarrhea
Fever
