Case based discussion

Pankaj MalhotraPGIMER, Chandigarh, India

Case History

• A 43-year old gentleman presented with weakness and fatigability x 3 months

• Hb 13.4 gm/dl, WBC 220,000 cells/mm3, Plat 679000 cells/mm3

• Spleen 10 cm• BM: Hypercellular, 8% blasts, Ph 20/20

positive, Q RT PCR for BCR ABL mRNA 80%• Sokal High-risk

Case History

• A 43-year old gentleman presented with weakness and fatigability x 3 months

• Hb 13.4 gm/dl, WBC 220,000 cells/mm3, Plat 679000 cells/mm3

• Spleen 10 cm• BM: Hypercellular, 8% blasts, Ph 20/20 positive,

Q RT PCR for BCR ABL mRNA 80%• Sokal High-risk• Availability of Imatinib/Dasatinib/Nilotinib

Choice of first line therapy Feb 2013

1. Imatinib 400 mg OD2. Imatinib 800 mg OD3. Dasatinib 100 mg OD4. Nilotinib 300 mg BD5. Nilotinib 400 mg BD6. Bosutinib 500 mg OD

Would Sokal high-risk score have impact on the choice of first line therapy?

Choice of first line therapy Feb 2013

1. Imatinib 400 mg OD2. Imatinib 800 mg OD3. Dasatinib 100 mg OD4. Nilotinib 300 mg BD5. Nilotinib 400 mg BD6. Bosutinib 500 mg OD

Does enough finances/insurance coverage impact on choice of first line therapy

Case History

• A 43-year old gentleman presented with weakness and fatigability x 3 months

• Hb 13.4 gm/dl, WBC 220,000 cells/mm3, Plat 679000 cells/mm3

• Spleen 10 cm• BM: Hypercellular, 8% blasts, Ph 20/20 positive,

Q RT PCR for BCR ABL mRNA 80%• Sokal High-risk• Active coronary artery disease and AF

Choice of first line therapy Feb 2013

1. Imatinib 400 mg OD2. Imatinib 800 mg OD3. Dasatinib 100 mg OD4. Nilotinib 300 mg BD5. Nilotinib 400 mg BD6. Bosutinib 500 mg OD

Would active coronary artery disease & AF impacts your decision making?

Case History

• A 43-year old gentleman presented with weakness and fatigability x 3 months

• Hb 13.4 gm/dl, WBC 220,000 cells/mm3, Plat 679000 cells/mm3

• Spleen 10 cm• BM: Hypercellular, 8% blasts, Ph 20/20 positive,

Q RT PCR for BCR ABL mRNA 80%• Sokal High-risk• Past history of pulmonary tuberculosis

Choice of first line therapy Feb 2013

1. Imatinib 400 mg OD2. Imatinib 800 mg OD3. Dasatinib 100 mg OD4. Nilotinib 300 mg BD5. Nilotinib 400 mg BD6. Bosutinib 500 mg OD

Would a past history of lung infection impacts your decision making?

Choice of first line therapy depends upon

1. Available finances/Full insurance2. Side effect profile of the drugs3. Co-morbid conditions of the patient4. Phase of the disease(Acc or BC)5. Sokal score (?)

Choice of first line therapy depends upon

1. Available finances/Full insurance2. Side effect profile of the drugs3. Co-morbid conditions of the patient4. Phase of the disease(Acc or BC)5. Sokal score (?)6. Physician preference/Patient preference (?)

Comparison of TKI

Favour Imatinib• Cheaper• Long-term experience• Known side effect profile• CCyR 70% at 1 year

• Less effective• More than 100 mutations

Favour 2nd G TKI• More effective • CCyR 80-85%• Fewer mutations (<10)

• Costly• Post marketing surveillance

suggest some unusual side effect

• Fewer options if disease progress

The patient was started on Imatinib 400 mg/day

Progress

• Achieved CHR by 2 months• RQ PCR for BCR-ABL at 3 months 22% IS

What are the long-term chances of PFS of this gentleman? ( RQ PCR >10% at 3 months)?

1. High2. Low

Progress

• Achieved CHR by 2 months• RQ PCR for BCR-ABL at 3 months 12% IS

What are the long-term chances of PFS of this gentleman? ( RQ PCR >10% at 3 months)?

1. High2. Low

The patient was started on Dasatinib 100 mg/day

Progress

• Achieved CHR by 2 months• RQ PCR for BCR-ABL at 3 months 12% IS

What are the long-term chances of PFS of this gentleman? ( RQ PCR >10% at 3 months)?

1. High2. Low

Thus with 2nd G TKI, you expect more rapid response, may be CCyR at 3 months/BCR ABL <2% at 3months

Assessment at 6 -months

• Glivec 400 mg/day continued• Hb 10.0 gm/dl MCV 102 WBC 3500 cells/mm3

Plat 100,000 cells/mm3• BM: Mild hypocellular• Cytogenetics 2/20 = MCyR• Q PCR 1% IS

What is your assessment and would you consider change in your strategy?

Current role of Allo HSCT

Conclusions

• Rapid advancement taking place in the field of CML

• Availability of many drugs have made life easy as well as difficult both for the physician as well as the patient

• Need to continue update our knowledge on CML on the basis of continuously emerging data