Guenther Koehne, MD, Highlights Recent Advancements in the Treatment of Blood Cancers – Oncology Learning Network

Transcript

The first bispecific antibody called blinatumomab, which is a CD30 antibody conjugated to a Tcell, has been explored now in combination with a thymidine kinase inhibitor to treat as induction patients with acute lymphoblastic leukemia.

Dexamethasone is also being administered there. It's an antibody conjugate.

It is a thymidine kinase inhibitor, which is specifically targeting leukemia cells, and then dexamethasone. There is no chemotherapy involved. Still, new reports, The New England Journal of Medicine just presented that you can get these patients into a complete remission.

Most importantly, and that's where my part comes in, or my heart, as a transplant physician, what turns out to be really critically important is that the induction therapy prior to allogeneic stem cell transplantation can affect the outcome posttransplant.

The reason why patients with acute lymphoblastic leukemia got infectious complications following transplant is not necessarily the conditioning regimen of the transplant itself, but it preceded with a strong chemotherapy that I alluded to before. Prior to the transplant, that posttransplant induced these complications.

If we can reduce that toxicity profile, then we may have a better outcome of allogeneic stem cell transplantation, which is still needed after the chemotherapyfree induction chemotherapy, but the risk of complications is hopefully reduced.

Whats exciting in ALL is chemotherapyfree, would be blinatumomab and thymidine kinase inhibitor, dasatinib, or ponatinib in combination with dexamethasone is exciting.

The integration of targeted therapies in acute myeloid leukemia with FLT3 inhibitors, IDH1, IDH2 inhibitors, very exciting.

Maybe we can, with that, reduce chemotherapy exposure as well. Also, likely, we'll hear about maintenance treatment of these higher risk diseases with these targeted therapies prolonging the progressionfree survival and the overall survival.

Relatively new now coming in is the development of the BCMA or Bcell maturation antigen directed therapies for multiple myeloma. This will also be revolutionary in the development of combinations for this particular disease.

With respect to stem cell transplantation, the opinion may be divided a little bit. I'm coming from Memorial Sloan Kettering Cancer Center. Before I joined Miami Cancer Institute, we already did a lot of what's called graft manipulation. Prior to the transplant, we reduced certain effector cells, particularly T lymphocytes that have otherwise the risk to induce graftversushost disease posttransplantation.

Our studies show promising outcome. Our studies also show that we don't need immunosuppressive therapy following transplant, which increases the quality of life of the patients going through this transplant process.

Not only of the side effect profile of these immunotherapy drugs, but they don't have to come to the hospital back twice a week just to monitor the levels, etc. That is exciting. I'm particularly working here on other forms of graft manipulation, which I believe will help to further improve the outcome.

The CAR Tcell or the CAR, development, I alluded to also. Now, we are moving toward more directed CAR Tcells. Dr. (Robert) Sackstein, again, with this modified attempt to increase the effectiveness of CAR Tcells at the tumor site will likely also be able to show in clinical trials that you can use less CAR Tcells than you need with unmodified cells.

With that, then, you would decrease the side effect profile of CAR Tcells, which is particularly known as cytokine release syndrome and neurotoxicity. That would certainly provide another benefit over existing CAR Tcell trials.

As I said before, now, we are focusing on using other effector cells that can be modified with the chimeric antigen receptor, such as NK cells, monocytes, and likely down the road, other cells that will help to improve the outcome of these therapies.

For me, personally, I really like to add it is exciting at this time of my career to have colleagues and friends around the world of this quality and world leaders that are excited to come and present at our Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies, and to really communicate with them.

Send one invitation and they just basically answer, "I'm in, I'm happy to come." Unfortunately, not in person this time, but it will be again next year in January. They will all come down to Miami and will join the third summit at that point, but now by Zoom. It's very exciting and rewarding for me.

To read Part I, click here.

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Guenther Koehne, MD, Highlights Recent Advancements in the Treatment of Blood Cancers - Oncology Learning Network