Revolutionizing AML Treatment: Innovative Targeted Approaches with Dr. Koehne

Dr. Koehne, the Deputy Director of Miami Cancer Institute, discusses the changing landscape of acute myeloid leukemia (AML) treatment, including the use of novel targeting agents for patients. He also introduces a new clinical trial utilizing CRISPR technology to create CD33 negative healthy stem cells for transplantation, allowing for targeted anti-CD33 therapies or CAR T-cell treatments for AML patients. The initial results show promise for improving patient outcomes.

Video Transcript

The AML landscape is significantly changing. For over 30 years we had two drugs that was called 7+3. 

Now we have novel, targeting agents that allow us to really impact the risk stratification of patients with acute myeloid leukemia from the very beginning. For example, today, we would not treat FLT3 positive AML or a TP53 mutated AML the same as a good risk AML.

My position here at Miami Cancer Institute allows me to stratify patients from diagnosis on rather than to wait for the leukemia doctor to send the patient for transplantation, because we know first published by Dr. Stone in the New England Journal of Medicine, for example, that the treatment before the transplant may also affect the outcome of the patient post transplantation. So, in other words, you can improve the outcome by doing the right thing before transplantation.

The RATIFY study focused on FLT3 positive AML. These patients received the FLT3 inhibitor midostaurin in combination with 7+3 chemotherapy. This led to more patients going into transplant and approved outcomes in patients who received the combination compared to patients who only received 7+3. This was just the beginning of risk stratification in AML. Now at my facility, we have a dedicated FDA approved clinical protocol for patients with FLT3 positive AML.

We have a dedicated clinical trial for patients with TP53 mutated AML, and we also have post transplantation strategies based on minimal residual disease (MRD) that allows us post transplantation to improve the outcome of patients.

Now, CAR T-cells for AML is a critical question. What can we target on AML cells? This is a little bit more difficult than in the other settings as acute lymphoblastic leukemia (ALL), or multiple myeloma, because AML molecules are shared between the leukemia cells and the normal hematopoietic stem cell. This limits us to target common targets such as CD33, because if we target CD33 and treat with CAR T cells, we will likely also eliminate the healthy hematopoietic stem cell, and if that occurs, patients will experience myelosuppression. This problem is currently being addressed. I'm happy to report that I am the principal investigator of a brand new clinical trial in which we collect and purify the transplant donor's hematopoietic stem cells in the laboratory and use CRISPR technology to silence the expression of CD33. This creates a product that is a healthy stem cell product that is CD33 negative. We then transplant the patient with the CD33 negative product, and as of now, the first few patients, have achieved a complete normal engraftment. This trial will then allow us to give anti CD33 directed CAR T-cells in the long run because the only cell that is positive for CD33 is an AML cell. This is a brand new approach that I think is highly innovative. The first indication that this is effective has been presented just two days ago at the ASTCT meeting in Orlando, Florida.

We will have a presentation at the EBMT meeting in Paris in a few weeks showing that the first three to four patients have a normal engraftment with CD33 negative stem cells and CD33 negative cells. We can target specifically any leftover leukemia cells with anti-CD33 approaches. In the long run, we are now working with a subsequent protocol to develop donor derived CAR T cells, specifically targeting the CD33 on the leukemia cells. 

To view more information about the AML clinical trials currently open at Miami Cancer Institute, visit HealthTree's 

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