Dr Elizabeth Griffiths on Biomarkers, Mutational Events That Drive Treatment Choice in AML

Elizabeth Griffiths, MD, associate professor of oncology, department of medicine, Roswell Park Comprehensive Cancer Center discusses which biomarkers and mutational events help determine if a patient would likely benefit from a traditional therapy or if they are more suitable for a clinical trial or upfront allogeneic transplantation.

TranscriptWhich biomarkers or mutational events help determine if a patient with acute myeloid leukemia (AML) would likely benefit from a traditional therapy or if they are more suitable for a clinical trial or upfront allogeneic transplantation?

I think the majority of us in the community would say that patients with complex karyotype or p53 mutant disease tend to fare less well with traditional induction approaches. I think in that patient population, I would be more likely to think about giving them a liposomal cytarabine and daunorubicin combination strategy, or even an alternative induction like a combination of azacitidine and venetoclax or decitabine and venetoclax.

Since their molecular profile tends to predict a poor response to standard therapy and, at least with the data that Daniel Pollyea, MD, MS, associate professor of medicine, University of Colorado School of Medicine, is going to present tomorrow, it seems as though those patients do a little bit better with this alternative combination strategy.

I don’t think that’s really ready to prime time, and I don’t think that’s supported, necessarily, by well-controlled data, but it’s certainly a feeling that many of us I think in the field have. If you have a young fit patient, I think one is compelled to really think strongly and offer the patient standard induction therapy, even if they have relatively poor-risk mutational features or cytogenetic risk profile, possibly with a combination of the liposomal combination therapy, since that appears to result in a better long-term outcome, especially in patients who are eligible for allogeneic transplant. And that would be the kind of patient where you would want to be able to offer an upfront allogeneic transplant.

With respect to upfront allogeneic transplant, I don’t think we would do that for patients with overt leukemic disease, unless they had really exhausted all other strategies. So, I wouldn’t do it upfront, but I might consider it if I have a patient who I’m able to get into a good, deep complete remission who has a high risk of relapse.