Chetasi Talati, MD
Chetasi Talati, MD, Assistant Member in the Department of Malignant Hematology at Moffitt Cancer Center, Tampa, Florida, commented on the study by Borthakur et al.
“[Core-binding factor] acute myeloid leukemia (AML) represents a favorable-risk group of patients who are more chemosensitive and may be able to be cured by chemotherapy alone. Gemtuzumab ozogamicin was taken off the market in 2010 due to liver toxicities, but a huge meta-analysis showed that if we dose it differently and combine it with chemotherapy, there is a survival benefit in patients with favorable-risk cytogenetics. Some centers use a 7+3 induction regimen of cytarabine plus anthracycline. FLAG-IDA has been the standard at MD Anderson,” Dr. Talati noted.
“The results of the comparison between the two regimens are intriguing. They raise the question of whether we cure patients with [core-binding factor] AML when we add gemtuzumab ozogamicin to FLAG. Overall survival was no different, but relapse-free survival favored FLAG-GO. The reason why survival was no different is because patients with residual disease undergo allogeneic transplant,” she explained.
Other Considerations and Implications
“The 7+3 regimen is more toxic than FLAG-GO, it takes longer to deliver, and it is only used in patients under age 70. In this study, 15% of patients were aged 65 or older. The presence of KIT mutations changes the risk from favorable to intermediate, and in this analysis, KIT mutations did not influence outcome. I interpret this as a positive finding, because if KIT status didn’t change the risk, these patients may not need transplant. If they have undetectable minimal residual disease (MRD), perhaps we can leave them alone,” she commented.
“Also, the inclusion of gemtuzumab ozogamicin in the chemotherapy backbone of FLAG results in higher relapse-free survival and similar overall survival, suggesting you can avoid using an anthracycline. The higher rate of relapse-free survival is likely due to the higher rate of MRD achieved by FLAG-GO, as reflected by the log reduction in fusion transcript ratio, which is a surrogate for MRD,” Dr. Talati said.
“The finding that gemtuzumab ozogamicin can be incorporated in an induction chemotherapy regimen is important, and FLAG-GO represents one of those regimens…. Another take-home message is the importance of MRD monitoring in AML. This should be the standard of care, because it can influence treatment decisions,” she stated.
DISCLOSURE: Dr. Talati has received honoraria from Agios, Celgene, Daiichi Sankyo, and Pfizer; and has participated in speakers bureaus for Astellas Pharma and Jazz Pharmaceuticals.
Gemtuzumab ozogamicin, once approved in 2000 for the treatment of acute myeloid leukemia (AML), was taken off the market in 2010 due to toxicity concerns. Idarubicin has been used in place of gemtuzumab ozogamicin in some chemotherapy regimens. Gemtuzumab ozogamicin was reintroduced to the market...