Patient Profiles
Patients With Signs of Intolerance
EARLY INTOLERANCE
How would you treat a patient who is experiencing early intolerance on their 2nd TKI?
Clinical Presentation and Medical History
50 years old
Diagnosed 6 years ago with Ph+ CML-CP
Comorbidities include diabetes managed with insulin
After ~5.5 years on his 1st TKI, he switched treatments due to loss of response
After 3 months on his 2nd TKI, he began experiencing a bothersome grade 3 rash and increased ALT/AST (signaling early intolerance), which had not resolved 4 months later
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): 7%
Brooks’ Story
Brooks is married, the father of 3 children, and best friend to the family dog. He enjoys being an active member of the community and has a financial planning practice with an office downtown.
Recently, he started a different Ph+ CML-CP treatment and has developed increased ALT and AST, as well as a bothersome grade 3 rash. As a result, he has withdrawn somewhat from his usual community activities and spends less time in town with his family.
His Latest Visit
His doctor said that while they understood Brooks had a rash, he was responding well to treatment. Brooks told his doctor the rash made it hard to meet with clients.
Review the tolerability data >
ALT, alanine transaminase; AST, aspartate aminotransferase; IS, International Scale; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.
PULMONARY ADVERSE REACTION
What’s your next move for a patient experiencing moderate and persistent* GI ARs on their 2nd TKI?
Clinical Presentation and Medical History
70 years old
Diagnosed 2 years ago with Ph+ CML-CP
Active dyslipidemia managed with a medication
After ~5 months on her 1st TKI, she switched treatments due to grade 3 edema
After 1 year on her 2nd TKI, she is experiencing grade 2 GI adverse reactions (diarrhea, nausea)
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): ≤0.1%
Ramona’s Story
Ramona retired about a year ago after a long career in real estate, which happened to coincide with starting a 2nd TKI. She has 6 grandchildren who live nearby and has become somewhat of a local legend at pickleball.
Her first year of retirement has been wonderful, but recently she has developed low-grade GI adverse reactions (diarrhea and nausea). Her doctor told her it’s just part of treatment, but she thinks twice now before taking her grandchildren off on an adventure, and she hasn’t been showing up at the courts as much.
Her Latest Visit
Ramona is responding well to her 2nd TKI. However, when her doctor asked her how she has been doing, Ramona shared that she has been much less active than normal. She said that she was concerned about leaving her house due to the diarrhea and nausea she has been experiencing during the last few months. She has tried over-the-counter medications to alleviate some of her symptoms, but they do not seem to be helping. Her doctor has also tried dose adjustment.
Review the tolerability data >
AR, adverse reaction; GI, gastrointestinal; IS, International Scale; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.
*Grade 2 toxicity that is unresponsive to optimal management, including dose adjustments.
SUBOPTIMAL RESPONSE AND INTOLERANCE
How would you treat a patient who is experiencing moderate and persistent* ARs on their 2nd TKI?
Clinical Presentation and Medical History
63 years old
Diagnosed 8 years ago with Ph+ CML-CP
History of controlled anxiety
After ~7 years on her 1st TKI, she switched treatments due to an adverse reaction (grade 2 fatigue)
After 1 year on her 2nd TKI, she is experiencing fatigue and diarrhea (both grade 2)
Her doctor told her to try an OTC medicine for her diarrhea, but it didn’t help. Dose adjustment also did not help
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): <0.1%
Maria’s Story
Maria is a grandmother of 2, a nurse, and a golfer—all of which keep her on her feet. She switched to her 2nd TKI about 1 year ago because of fatigue, but now she once again finds herself experiencing fatigue and diarrhea.
She’s no longer comfortable being out on the golf course or having her grandchildren visit on their own, and she has started to take fewer shifts at the hospital.
Her Latest Visit
Maria told her doctor she was doing some research online and read somewhere that she might be able to take her medicine every other day instead of every day. She asked if doing that might affect how well her medicine is working.
Review the tolerability data >
AR, adverse reaction; CCyR, complete cytogenetic response; IS, International Scale; OTC, over the counter; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.
*Grade 2 toxicity that is unresponsive to optimal management, including dose adjustments.
Patients with suboptimal responses
EARLY LACK OF RESPONSE
What would be the next step for a patient with a suboptimal response on their 2nd TKI?
Clinical Presentation and Medical History
42 years old
Diagnosed 3 years ago with Ph+ CML-CP
After 4 years on his 1st TKI, he switched treatments due to loss of response
After 6 months on his 2nd TKI, his BCR::ABL1 transcript levels are still greater than 10% (signaling a lack of response)
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): 10.1%
Patient underwent a mutational analysis; no resistant mutation was identified
Jim’s Story
Jim is a physical therapist, a runner, and the coach of his 12-year-old son’s soccer team. He began treatment for Ph+ CML-CP a few years ago but had to switch treatments due to a loss of response.
Now on his 2nd TKI, he is facing another possible loss of response.
His Latest Visit
Jim’s doctor suspected an issue and asked him if he was experiencing any side effects that impacted his daily life.
IS, International Scale; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.
SUBOPTIMAL RESPONSE
How would you help a patient with a suboptimal response on their 2nd TKI?
Clinical Presentation and Medical History
51 years old
Diagnosed with Ph+ CML-CP 5 years ago
Occasional GERD treated with a PPI
After 4 years on his 1st TKI, he switched treatments due to loss of response
After 1 year on his 2nd TKI, he has not achieved CCyR (signaling a suboptimal response)
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): 5%
Patient underwent a mutational analysis; no resistant mutation was identified
Apollo’s Story
Apollo is a high-school English teacher. He lives with his partner and 2 sons and leads a book club that meets at the library. He was on his 1st TKI for 4 years before experiencing a loss of response. The same thing happened on his 2nd TKI, but after only 1 year.
His Latest Visit
Apollo expressed frustration and considerable anxiety about being unable to achieve an adequate response to treatment.
CCyR, complete cytogenetic response; GERD, gastroesophageal reflux disease; IS, International Scale; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; PPI, proton-pump inhibitor; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.
Patients with the T315I mutation
How would you treat patients who have the T315I mutation?
Clinical Presentation and Medical History
40 years old
Diagnosed 1 year ago with Ph+ CML-CP
After experiencing resistance on her 1st TKI, she had a mutational analysis
Ponatinib naive
Recently tested positive for T315I mutation
Quantitative RT-PCR (qPCR) using IS for BCR::ABL1 (blood): 9%
No other past medical history or comorbidities
Family history of acute myocardial infarction
Has been on her 1st TKI for 1 year
Patient achieved BCR::ABL1 transcript levels of 6% at 6 months
Lily’s Story
Lily is a restaurant manager who lives with her husband. A year after being diagnosed with Ph+ CML-CP, she found out that she has the T315I mutation, which can be more challenging to treat.
Her Latest Visit
At 12 months, Lily has not achieved CCyR and her BCR::ABL1 transcript levels have increased to 9%. She recently underwent a mutational analysis and tested positive for the T315I mutation.
Learn more about the T315I mutation >
CCyR, complete cytogenetic response; IS, International Scale; Ph+ CML-CP, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase; RT-PCR, reverse transcription polymerase chain reaction; TKI, tyrosine kinase inhibitor.