After starting TKI treatment, blood cell counts including differential blood counts should be performed every other week until a complete hematologicical response is achieved. At 3 months and every 3 months thereafter (at least until achieving a MMR or MR3), a quantitative measurement of BCR-ABL on blood cells according to the international scale (BCR-ABL
IS) should be done [
8]. Ideally, a BCR-ABL
IS of ≤ 10% should be achieved after 3 months to be termed “optimal response”. If a value of BCR-ABL
IS of > 10% is confirmed within the next following 3 months, TKI therapy must be changed to an alternative TKI. If a mutation within the BCR-ABL kinase is detected under these circumstances, the following TKI must be sensitive to the detected mutation. In case of the availability of various sensitive TKIs, the best suitable TKI according to existing comorbidities can be chosen. If no BCR-ABL kinase mutation is detected, any other available TKI can be taken. In the case that the initial CML therapy was started with imatinib, this should be a 2ndG TKI. If, however, CML therapy was already started with a 2ndG TKI, one should strongly consider using the 3rdG TKI ponatinib if no cardiovascular risk factors preclude its use [
8], as data from the 3rd line setting strongly suggest a low likelihood of a long-term response of a 2ndG TKI after a 2ndG TKI [
16]. In contrast to the initially FDA (US Food and Drug Administration) approved dose of 45 mg per day, the 2020 ELN guidelines strongly recommend to start with a lower dose of 30 mg or even 15 mg to avoid cardiovascular toxicity except in patients with T315I, compound mutations or progression to an advanced phase [
8]. This suggestion from the ELN is supported in part from recent results of the OPTIC study, showing that a starting dose of 30 mg ponatinib is equally effective to the 45 mg dose if no mutation is present or if ≤ 2 prior TKIs were used. Moreover, the study also revealed that the ponatinib dose can be further reduced to 15 mg if a BCR-ABL
IS value of ≤ 1% is achieved [
17].
In case of intolerance, every other available TKI can be considered.