Optimizing use of TKIs in CML
“If you disregard toxicities, I think ponatinib is the most powerful TKI, and I think that’s because we are using it at a higher dose that produces so many toxicities,” Dr. Kantarjian said.
He added that the reason ponatinib is not used upfront is because of these toxicities, particularly pancreatitis, skin rashes, vaso-occlusive disorders, and hypertension.
Dr. Kantarjian suggests giving ponatinib at 30 mg daily in patients with T315I mutation and those without guiding mutations who are resistant to second-generation TKIs.
When to discontinue TKIs
Dr. Kantarjian said patients can discontinue TKI therapy if they:
- Are low- or intermediate-risk by Sokal
- Have quantifiable BCR-ABL transcripts—B2A2, B3A2 (e13a2 or e14a2)
- Are in chronic phase
- Achieved an optimal response to their first TKI
- Have been on TKI therapy for more than 8 years
- Achieved a complete molecular response (MR4.5)
- Have had a molecular response for more than 2 to 3 years
- Are available for monitoring every other month for the first 2 years.
Dr. Kantarjian did not report any conflicts of interest at the meeting. However, he has previously reported relationships with Novartis (makers of imatinib and nilotinib), Bristol-Myers Squibb (makers of dasatinib), Pfizer (makers of bosutinib), and Ariad Pharmaceuticals (makers of ponatinib, now owned by Takeda Pharmaceutical Company Limited).
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