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AML Treatment Additions Encouraging, But MDS Landscape Still Facing Challenges

Angelica Welch
Published: Saturday, Mar 31, 2018

One of the most exciting developments in the elderly population is the data that have come out about the addition of venetoclax to either hypomethylating agents or low-dose cytarabine. There was a paper from researchers at The University of Texas MD Anderson Cancer Center on it in combination with hypomethylating agents, and at the 2017 ASH Annual Meeting we saw how it could be combined with low-dose cytarabine.

When you look at the combination, we are using the standard doses of our gentle drugs—hypomethylating agents and low-dose cytarabine. Venetoclax is extremely well tolerated, and more importantly, we are seeing a 60% complete response rate. This is pretty much unheard of with low-dose therapies. We are hoping that this may be a big step forward for the elderly patient who is not appropriate for aggressive induction chemotherapy. 

Can you discuss the current treatment approach for relapsed/refractory patients?

Once a patient with leukemia relapses, and if you are trying to cure the patient, the goal is transplant. We have years of experience of trying to get them to transplant safely with less toxicities, but it has been a challenge. We don't have a standard second go-to therapy. However, we do have a couple developments in targeted therapies, such as second-generation FLT3 inhibitors and IDH1/2 inhibitors, which are well tolerated and allow the patient to have good quality of life, and potentially get them to transplant. Now we have gemtuzumab ozogamicin, which has been brought back. It may not be appropriate in the pretransplant setting, because it may raise the risk of veno-occlusive disease, but for patients not going to transplant, it may offer a lower-dose solution. 

What is the current treatment landscape of MDS?

Although there is a lot of excitement about what has happened in the past year in AML, we have gone another year without developing anything new for MDS. The therapeutic options continue to be fairly limited. There are a couple drugs on the horizon. 

Then, there is clonal cytopenia of uncertain significance (CCUS). This is where the patient has low blood counts and bad genetics, but not the dysplasia to call it MDS. We have spent some time defining these characteristics in patients who might develop MDS in the future, but unfortunately, we still do not have treatments for them. This at least gives us a little more guidance on who we should watch and how we should follow them.

What is the greatest unmet need you would like to see addressed in both AML and MDS?

One of the greatest unmet needs is treating AML in the elderly. Despite all of this encouraging data, survival for the elderly patient has not changed in the last 20 to 30 years. We know that AML is a disease traditionally of the elderly. We have made some great headway this past year with new drugs, but we are still focused on the fit patients. Hopefully, the potential addition of venetoclax will help the elderly patients. 

Similarly, we have gone a decade without any new advances in MDS, which is also an elderly population. This is where we need to focus our efforts from a research standpoint. Hopefully, understanding the genomics—which has exploded into the hematologic malignancies field—will point us in new directions. 

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TitleExpiration DateCME Credits
Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing StrategiesMay 31, 20191.5
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