CML

Question 1

What is the hallmark translocation in CML?

Answer 1

t(9;22) BCR/ABL gene

Question 2

What are side effects of Imatinib?

Answer 2

Myelosuppression, Fluid retention, edema, skin rash, renal abnormalities, weight gain, muscle aches, diarrhea

Question 3

What are the side effects seen with Nilotinib?

Answer 3

Rash, headaches, increased T. Bili, increased blood sugar, renal issues, pancreatitis, VOC (CVA, MI), QT prolongation

Question 4

What are the side effects seen with Dasatinib?

Answer 4

Myelosuppression, pleural effusion, Pulm HTN, platelet dysfunction

Question 5

What are the side effects of Bosutinib?

Answer 5

Myelosuppression (more thrombocytopenia), D/N/V, pancreatitis, renal, and transaminitis.

Question 6

What is the indication for Ponatinib? Third gen TKI

Answer 6

Resistance or intolerance to at least two prior kinase inhibitors OR with a T3151 mutation! Please don’t forget that.

Question 7

What are the side effects seen with Ponatinib?

Answer 7

Thrombocytopenia, rash, dry skin, HTN, abdominal pain. Arterial occlusive events-CVA, MI, PAD.

Question 8

In the first 3 months of TKI therapy what is the goal BCR/ABL transcript? At what time point is it a tx failure?

Answer 8

It should be less than 10%. You can proceed with caution if they aren’t prior to this, but by 6 months if they aren’t this is a treatment failure

Question 9

What is the BCR/ABL transcript goal at 12 months?

Answer 9

Less than 0.1%

Question 10

If a patient is at 1-10% BCR/ABL transcript at 1 year what is the best next step in management? High Yield

Answer 10

Evaluate for drug to drug interaction, patient compliance, check cytogenetic studies, and send for mutational analysis. You can either switch to a new TKI or keep the same if a CCyR is achieved

Question 11

If a patient has a BCR/ABL transcript greater than 10% at 6 months or 1 year what is the best next step in management? High yield!

Answer 11

Switch to alternate TKI and evaluate for allogeneic SCT. Also want to check for patient compliance and send for mutational analysis. They have to switch therapy in this situation!

Question 12

If a patient has a BCR ABL of 0.1-1% at one year what is the best next step in management?

Answer 12

If long term survival is the goal-continue same TKI
If treatment free remission is the goal, should consider switching to get it to less than 0.1%.

Question 13

Is imatinib contraindicated in pregnancy?

Answer 13

Yes due to fetal malformations

Question 14

What is the tx for advanced phase CML?

Answer 14

Second gen TKI-Bosutinib, Dasatinib, or Nilotinib
Third gen TKI-Ponatinib All of these options are preferred. Can obviously use Imatinib if the above are contraindicated. Also have the option of Asciminib. If they continue to progress past this point then you need to do allo-SCT.

Question 15

What is the definition of advanced phase? Blast phase?

Answer 15

15-29% blasts in the bone marrow or periphery. Peripheral blood basophils of 20% or more. Thrombocytopenia unresponsive to therapy less than 100K. Cytogenetic evidence of clonal evolution. Promyelocytes and myeloblasts combined at 30% or more.
Blast Phase: 30% or more blasts in the BM or periphery. Extramedullary infiltrates.

Question 16

What is the treatment approach for blast phase?

Answer 16

You start preferably a 2nd or 3rd gen TKI plus chemo (depending on if ALL vs AML). ALL-e.g. HCVAD. AML-Decitabine, Aza, FLAG-IDA

Question 17

Remember that exon 14A2 is the most common p210 transcript over exon 13A2.

Question 18

Know that a deep molecular response at 18 months correlates with a superior EFS, but no benefit with OS or rate/survival of transformation to advanced or blast phase.

Question 19

What is the first line tx for a patient with chronic phase CML that has a low risk score?

Answer 19

1st gen-Imatinib (Cat 1)
2nd gen-Bosutinib, Nilotinib, Dasatinib (all Cat 1 options)
Asciminib (Cat 1) (cannot used in those lacking exon 13A3 and 14A3)
Clinical trial

Question 20

What is the first line tx for a patient with chronic phase AML that has a intermediate or high risk score?

Answer 20

2nd gen TKI: Bosutinib, Nilotinib, Dasatinib (all Cat 1 options)
Asciminib (Cat 1, cant use in exon 13A3, 14A3)
Other: Imatinib (1st gen), may be preferred in older patients and/or those with cardiovascular co-moribidities

Question 21

A complete cytogenetic response is defined as BCR/ABL transcript at less than 1% by 1 year. A major molecular response is defined as less than or equal to 0.1% A deep molecular response is defined as less than or equal to 0.01% or less than or equal to 0.0032%

Question 22

If a patient develops a T13531I mutation what TKI can you consider

Answer 22

Ponatinib or Asciminib (200mg BID as opposed to 40mg BID)

Question 23

When is a Allo-SCT recommended in CML

Answer 23

In those who progress and/or have intolerance on all TKIs in chronic phase, those that progress to advanced phase, and those in blast phase who achieve a morphologic response.

Question 24

For those w/o a mutation what are the best options in second and third line?

Answer 24

Ponatinib or Asciminib

Question 25

Omacetaxine is approved in those patients who have had resistance to 2 or more TKIs.

Question 26

What is the best next step in myelosuppression with Imatinib?

Answer 26

Hold for ANC less than 1K and Plt less than 50K. Check weekly CBC. If less than 2 weeks counts recover you can continue the same dose. If it takes longer you should decrease the dose.

Question 27

Remember that all the 2nd gen TKIs are assoc with cardiovascular/CVA side effects, but Nilotinib and Dasatinib are the highest and Bosutinib is the lowest. Also Asciminib has a much lower risk of these events compared to 2nd gen TKIs

Question 28

TKI withdrawal syndrome manifests as musculoskeletal symptoms (muscle/joint pain) and can be treated with NSAIDs or analgesics. You can decrease the risk of this by reducing the dose before stopping it

Question 29

How do you manage a pregnant patient w/CML diagnosed in the chronic phase?

Answer 29

If you will treat you can use Interferon alpha, after 16 weeks you can use Nilotinib or Imatinib. For very high WBC you can do leukapheresis. Per ELN recommendations, you can observe if they are asymptomatic and have WBC less than 100K and those with low or intermediate risk disease.