Table 3 Informed decision-making for TFR... | American Society of Hematology

Table 3

Informed decision-making for TFR candidates: practical examples

Case summary	Recommendation
Case 1: A 58-year-old woman has been taking imatinib 400 mg daily for 10 years. She has ongoing mild myalgia and arthralgia, but overall she reports that her quality of life is as good as that of many of her friends. She has maintained UMRD for 8 years.	In favor of a cessation attempt. Informed that there is a >50% likelihood that TFR could be achieved, but that the risks of stopping need to be weighed carefully against the risks of continuing, which in this case were very low. She decided not to stop TKI at this stage, saying that imatinib had been a normal part of her life for many years. Stopping imatinib would mean having more frequent blood tests, which she saw as an inconvenience with no meaningful gain. She was worried about the hypothetical risk that a period off therapy might lead to a loss of sensitivity to imatinib, arguing that even if this risk is small it is a risk that she need not take.
Case 2: A 78-year-old man treated with CML on imatinib 400 mg daily for 6 years. He has never achieved UMRD, but has maintained MR4.0 for the last 2 years. He is considering TKI cessation because of side effects (diarrhea and anemia).	In favor of a cessation attempt. Chances of TFR may be <50%, because he has received <8 years of TKI therapy and has only achieved MR4.0. However, he has substantial side effects, which in this case would be sufficient justification for a cessation attempt. Counseling here is important so that he understands the high probability that TKI withdrawal will not be successful.
Case 3: A 31-year-old woman with CML diagnosed 4.5 years ago. She received imatinib 600 mg daily for 2 years and then switched to nilotinib due to failure to achieve MMR. She rapidly achieved MR4.5 on nilotinib, which she has now maintained for 2 years.	Against proceeding with a cessation attempt at this stage. Recommended persisting with nilotinib for another 2 years and then consider a cessation attempt. The probability of TFR at this stage given the poor response to imatinib and the relatively short total duration of TKI is likely to be <50%. A premature attempt may significantly delay the time when she can successfully achieve TFR. Recognizing that fertility declines rapidly past the age of 30, there is a significant risk that the patient will go ahead without physician support and adequate monitoring. Some clinicians would stop TKI and use IFN as maintenance therapy in this situation.

Case summary	Recommendation
Case 1: A 58-year-old woman has been taking imatinib 400 mg daily for 10 years. She has ongoing mild myalgia and arthralgia, but overall she reports that her quality of life is as good as that of many of her friends. She has maintained UMRD for 8 years.	In favor of a cessation attempt. Informed that there is a >50% likelihood that TFR could be achieved, but that the risks of stopping need to be weighed carefully against the risks of continuing, which in this case were very low. She decided not to stop TKI at this stage, saying that imatinib had been a normal part of her life for many years. Stopping imatinib would mean having more frequent blood tests, which she saw as an inconvenience with no meaningful gain. She was worried about the hypothetical risk that a period off therapy might lead to a loss of sensitivity to imatinib, arguing that even if this risk is small it is a risk that she need not take.
Case 2: A 78-year-old man treated with CML on imatinib 400 mg daily for 6 years. He has never achieved UMRD, but has maintained MR4.0 for the last 2 years. He is considering TKI cessation because of side effects (diarrhea and anemia).	In favor of a cessation attempt. Chances of TFR may be <50%, because he has received <8 years of TKI therapy and has only achieved MR4.0. However, he has substantial side effects, which in this case would be sufficient justification for a cessation attempt. Counseling here is important so that he understands the high probability that TKI withdrawal will not be successful.
Case 3: A 31-year-old woman with CML diagnosed 4.5 years ago. She received imatinib 600 mg daily for 2 years and then switched to nilotinib due to failure to achieve MMR. She rapidly achieved MR4.5 on nilotinib, which she has now maintained for 2 years.	Against proceeding with a cessation attempt at this stage. Recommended persisting with nilotinib for another 2 years and then consider a cessation attempt. The probability of TFR at this stage given the poor response to imatinib and the relatively short total duration of TKI is likely to be <50%. A premature attempt may significantly delay the time when she can successfully achieve TFR. Recognizing that fertility declines rapidly past the age of 30, there is a significant risk that the patient will go ahead without physician support and adequate monitoring. Some clinicians would stop TKI and use IFN as maintenance therapy in this situation.