CTA: Are there particular sequences of treatments you find to be more efficacious than others? How do you select the best TKI therapy for a specific patient?
Dr Jabbour: No, I make front-line treatment generic imatinib and second-line treatment dasatinib or nilotinib. The choice is made based on patient comorbidities and mutation profiles. Because when a patient’s treatment fails, they acquire mutations, and some mutations are more specific to 1 therapy over the other.
The second issue is comorbidities. Somebody, for example, with a history of heart attack or somebody with diabetes or with vascular problems is not the best candidate for nilotinib given that nilotinib can cause vascular problems. In that instace, I give the patient dasatinib. In contrast, a smoker with lung injuries is at risk of pleural effusion, in that case I would avoid dasatinib and go for nilotinib. That’s my sequence.
CTA: How do you monitor treatment response? Are more biomarkers in development?
Dr Jabbour: There are 2 approaches. First, we try to have a profile and a baseline for patients’ first response. If a patient has a gene signature that tells us they are at high risk of progression, they might be able to get a newly approved drug or a combination. If a patient is at low risk, they get imatinib.
RELATED: Post-transplant Maintenance TKI Therapy Feasible for High-risk Ph+ Leukemia
Second, when a patient’s treatment is failing, you check for acquired mutations. If there are clones at low levels with mutations, there are ways to detect them, but it’s still experimental.