CTA: When is it time to switch therapies?
Dr Jabbour: The goal of CML therapy with standard-dose imatinib is to achieve complete cytogenetic response (CCyR) within 12 months and to maintain it. For second-generation TKIs, it may be important to achieve CCyR sooner, within 6 months. Patients who do not achieve a complete response by 3 months should be considered for a change in therapy. If patients still have greater than 10% BCR-ABL1 transcripts at 6 months, the chances of attaining CCyR are low, and a change in therapy might be indicated here as well.
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CTA: What factors are known to cause tumor TKI resistance?
Dr Jabbour: First of all, it has been shown that if a patient does not have certain genes at baseline, they will not do as well. But it’s not yet standard of care; it’s still very experimental. Second, there is 1 type of the BCR/ABL oncoprotein called b2a2 that is bad. It is more resistant to imatinib than the others. Third, there are other mutations a patient can acquire that may affect responses—often for unknown reasons, perhaps related to drug absorption or metabolism, or other factors.
CTA: At what point do you check on acquired genetic mutations?
Dr Jabbour: I check every time there is evidence of resistance. If the patient’s disease is not responding to treatment, I check for genetic mutations.
CTA: How big of a concern is dosing noncompliance by patients?
Dr Jabbour: I find that young patients are less compliant than older patients and I usually prefer once-a-day regimens over twice daily, partly for that reason.
CTA: What is the current role for allogeneic stem cell transplant (allo-SCT) in CML?
Dr Jabbour: In chronic phase CML, it is a last resort. The number of patients undergoing allo-SCT has decreased since TKIs were introduced. Allo-SCT remains an important option for patients with chronic phase CML who fail 2 or more TKIs or harbor the T3151 mutation. Allo-SCT is more important when patients evolve into accelerated- or blastic-phase CML. Patients with blastic-phase disease are most likely to benefit.
RELATED: Promising Secondary Endpoints for Ponatinib in CML Despite Early EPIC Trial Termination
CTA: What’s the most important issue facing the field today?
Dr Jabbour: Price, price, price. The price of the medicines is too much.2
References
- Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol. 2016;91(2):253-265.
- Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121(22):4439-4442.
