Second line therapy in

CML
Dr Pallabi Dash
Story so far…
46 years old female diagnosed as CML in CP

1st line treatment – Imatinib since 2009

Optimal response for 13 years

complains of fatigue for 4 months- April 2022

 Secondary resistance

Dose escalation in Imatinib

Admitted to CHW in poor condition- Aug 2022

What Next?
Second line therapy
Indications of second line therapy
Primary resistance

Secondary resistance

Warning state during follow up

Intolerance to first line therapy

Mutations specific treatment

Monitoring response to treatment
Depending on BCR-ABL1 transcript % on the International Scale (IS)*

36.8% in our
case!!!
* ELN 2020
Reason of failure
Poor adherance
Patient factor
Drug factor
KD mutations
T315A
F317L
BCR-ABL1-independent
Mutations ASXL1
RUNX1
TP53
Additional cytogenic trisomy 8
abnormalities isochromosome 17q
trisomy 19
 Mutation
analysis

Drug Toxicity
interactions profile of TKI

Clinical
considerations

Comorbid Patient age,

conditions. ability to
tolerate
therapy
Options for 2nd line therapy
1. Dose escalation
Imatinib - up to 800 mg daily
For cytogenetic relapse in patients with
previous cytogenetic response

Disadvantages
Duration of responses has typically been short
TIDEL-II study- switching directly to Nilotinib had
higher rates of MMR and complete molecular
response at 12 months than dose escalation of
Imatinib
2. Switching over to other TKI
3. Omacetaxine
Resistance to more than 2 TKIs
T315I mutation
4. Asimicinib

Allosteric inhibitor
4. Allogeneic stem cell transplant
Management of our case

Chemotherapy Dasatinib AlloSCT

Adhere
Monitor
Switch
Transplant
 REFERENCE
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