Updates on Recent Advances and Treatments for Hematologic Malignancies

Guenther Koehne, MD, PhD

With the increasing frequency of almost all diseases covered by hematologic malignancies, many questions and new ideas are constantly being answered and addressed for patients and physicians. As a result, a 2-day symposium, the Summit of the Americas on Immunotherapies for Hematologic Malignancies, was created to provide an overview of the most recent advances in hematologic oncology.

During the meeting, 25 experts joined director of the Summit of the Americas on Immunotherapies for Hematologic Malignancies, Guenther Koehne, MD, PhD, for the opportunity to discuss and learn about some of the new developments in the treatment of patients with leukemia, lymphoma, multiple myeloma, and stem cell transplantation and more.

Presentations highlighted at this year's meeting included discussions on several novel immunotherapies, new combinations, and even updates on the evolving field of molecular-based therapies.

“The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches,” Koehne, deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, said in an interview with Targeted Oncology^TM.

In the interview, Koehne provided an overview of The Summit of Americas on Immunotherapies for Hematologic Malignancies and some of the recent and exciting advances being seen in the hematology space.

Targeted Oncology: Can you explain the purpose of The Summit of Americas on Immunotherapies for Hematologic Malignancies?

Koehne: The title of the conference gives away a little bit. It's a global summit on immunotherapies for hematologic malignancies. The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches.

In all diseases that are covered by hematologic malignancies, that is acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, multiple myeloma, each of these diseases have specific drugs or combinations of drugs with an antibody that can specifically target tumor cells without targeting healthy cells, which wouldn't be the case with chemotherapy and chemotherapy combinations that we've been given before. Now, with the rapid development, there are so many questions that we've tried to answer or at least address. We cannot answer all of them because of the rapidity of the development. But for example, is 1 immunotherapeutic drug enough to get the patient into long lasting remission? Or should we combine them, or should we sequence them? Then there's still the follow-up question of when to provide the patient or send them for a stem cell transplantation, which would be an autologous stem cell transplantation for multiple myeloma or donor-derived allogeneic stem cell transplantation for patients with leukemia. As of now, that is still the only curative therapy that we have.

We also know that the patients should be in a complete remission. Particularly now we have very sensitive tests that we summarize as minimal residual disease, MRD, testing. We know that patients that are MRD-positive before an allogeneic stem cell transplant for acute myeloid leukemia, do as well as those that are MRD-negative. Now with these new approaches and targeted therapies, we are trying to get them into a complete remission before sending them to the allogeneic stem cell transplantation. All these topics are addressed [at this meeting] and they are important to answer.

What ongoing research has recently caught your eye in the hematology field?

I'm the principal investigator for a lot of new clinical trials specifically addressing FLT3-mutated acute myeloid leukemia, TP53-mutated myeloid leukemia, and I have a lot of trials in the workup for multiple myeloma. I'm leading 1 exciting clinical trial now that for the first time utilizes the CRISPR technology, which is molecular silencing and therefore down regulating the CD33 expression on hematopoietic stem cells. With that, we can now transplant patients with acute myeloid leukemia with CD33-negative hematopoietic stem cells. One may ask, why is that important? Because CD33 is also expressed on leukemia cells. The reason why we cannot target specifically acute myeloid leukemia with CAR T cells, or with any specific CD33 targeting antibodies, is that you would also target the healthy hematopoietic stem cell at the same time.

To prevent this, we can downregulate and transplant the patient with CD33-negative stem cells, and everything that is left after transplantation expressing CD33 is then the leukemia cells. With that, we have a specific targeting approach for this patient population as well. We have successfully transplanted 3 patients with these CD33-negative stem cells, and we can prove at this point that it's safe. We can follow up with immunotherapies for these patient populations, and that is clearly exciting and accompanied new levels of immunotherapeutic approaches in our view.

Wonderful, and are there any other future advances in the hematologic malignancy field that you're excited about?

Multiple myeloma has a lot of interesting developments right now with the so-called bispecific antibody treatments of the CAR T-cell treatments, specifically, in this case, targeting the B-cell maturation antigen or BCMA. That will lead to long-term maintenance of remissions.

I believe that will also add this topic of the discussion here at this meeting now, because with the CAR T cells or bispecific antibodies that specifically get the patients into a remission again, what is the role of autologous stem cell transplantation? In this scenario, do we still need autologous transplant or what would be the best timing for autologous stem cell transplantation in patients with multiple myeloma? It is an ongoing discussion. I personally believe that autologous stem cell transplantation still has a good and important role in maintaining a long-lasting relationship with these patients, with the CAR T cells that we have, or with the bispecific antibodies that we have and we can bring patients back into remission.

These remissions have a limited duration, so that indicates to me that 1, achievement of the complete remission patient should then be consolidated with autologous stem cell transplantation, which leads to more transplants than we had before because you don't transplant patients if they don't necessarily have a good remission.