Treatment Options Continue to Evolve for Hematologic Malignancies

With the advancement of new techniques, different combinations, adjusted regimens, induction timing, dosing levels, and more, outcomes for patients with difficult-to-treat hematologic malignancies have continued to improve.

Particularly for patients who have relapsed disease, a number of viable options are available, including chimeric antigen receptor (CAR) T-cells, bispecific antibodies, immunotherapeutic approaches, antibody conjugates, chemotherapy-free inductions, and multi-drug combinations. However, these therapies bring their own complications adding to the complexity of providing patients with the best form of care.

As a result, some of the nation’s top experts in the field came together at Miami Cancer Institute’s Third Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies, held April 8-9, 2022. During the meeting, physicians discussed recent advances in multiple spaces, consisting of leukemia, lymphoma, multiple myeloma and stem cell transplantation.

Due to the volume of new information in this field, the Summit works as a place where research can be shared between individuals. Experts are able to familiarize themselves with the most recent strategies and immunotherapies they may otherwise be unaware of. The next Summit is scheduled for March 2023.

During an interview with Targeted Oncology^TM, Gunther Koehne, MD, PhD, director of the Summit of the Americas on Immunotherapies for Hematologic Malignancies, and deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, explained the need to get experts together and discuss the increased activity of new developments in the space and how the Summit of Americas on Immunotherapies for Hematologic Malignancies is the perfect place for this discussion.

TARGETED ONCOLOGY: What was the purpose for the creation of the Summit of Americas on Immunotherapies for Hematologic Malignancies?

Koehne: This was the third Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies. There is a strong need to get experts together that are familiar with the new developments of immunotherapies and combination therapies for hematologic malignancies. There's a lot of activity and new developments right now for hematologic malignancies, which includes acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, non-Hodgkin lymphoma, and even in myelodysplastic, and myeloproliferative disorders. There is this necessity to have [this] and I'm happy to announce that we have the top leaders in all of these respective fields in 1 room to discuss and bring forward the new information that is needed to optimize the care for patients.

What successes were seen last year and how do you hope to improve the summit?

Last year's conference was by zoom, and we got together on a larger international scale with participants all over the world. However, it was limited to 4 or 5 presentations because of the restraints that we had.

The success, similar to what we have now, was extraordinary by bringing everybody up to date with respect to the developments and the clinical trial designs that are ongoing. This year, we built on it. We updated the first results of clinical trials that have been proposed a year ago, and we are coming together in person, which to my mind makes a difference.

Which topics discussed this year did you find to be the most exciting?

There are a lot of new developments Based on the selection of the speakers, I mean, it's extraordinary to have Richard Stone from Dana-Farber update us on the development of acute myeloid leukemia developments to integrate the novel therapies into the treatment. We have Hagop Kantarjian, who has been the leader in acute lymphoblastic leukemia for many years who was participating in person. We have Dr. Wendy Stock from [the] University of Chicago that will update us on acute lymphoblastic leukemia. Those are all exciting presentations and events.

We will focus on novel developments for the treatment of multiple myeloma with an emphasis on B-cell maturation antigen targeted therapies or BCMA. Targeted therapies that will be presented by a series of speakers, including Dr. Adam Cohen from the University of Pennsylvania. Paul Richardson from Dana-Farber Cancer Institute will give us an update on all of the developments in combination therapies for multiple myeloma. There are lots of new developments in the treatment of diffuse large B-cell lymphoma that will be presented. But particularly I'm interested when excited about updating the audience about the developments of the CAR T-cell therapies.

Michel Sadelain, who was the first with Carl Jung at the time from the University of Pennsylvania, to develop CAR T-cell therapies. I've been a longtime colleague of Michel Sadelain. During my time at Memorial Sloan Kettering Cancer Center, I remember very well the first time when he walked into the room and proposed an idea of modifying T cells with an antibody. That was way before we call them CAR T cells or chimeric antigen receptor T cells. He will give us a keynote address and update on the future of CAR T-cell therapies.

This also raises the question, how do the CAR T cells fit into the landscape of stem cell transplantation? And will it affect it in a sense that we do not need transplants anymore or whether it affected that we may even be able to do more transplants, which I believe are off because with CAR T-cell therapies, we can get more patients back into remission, [and] follow up with a transplant. So that is my friend from Dana-Farber Cancer Institute, who's the chief of Transplantation, Robert J. Soiffer, MD, who will pick up on this topic, which I think is critical to address.

I’m very excited to have Siddhartha Mukherjee, MD, who not only has won the Pulitzer Prize for writing the novel, The Emperor of All Maladies, and is now I'm working with him on a clinical trial that he proposed by having the marker on the hematopoietic stem cells silenced, which is called CD33, so that it's not expressed on the hematopoietic stem cells anymore. Then we can do a transplant from a donor with CD33-negative stem cells, which leaves us post-transplantation with CD33-positive cells that are likely the leukemic population. That we can specifically target these CD33 acute myeloid leukemia cells post transplantation. He presented his idea and the clinical trial that I'm participating in.

Altogether, I think that in the CAR T-cell field in association with stem cell transplantation, there is going to be a lot of activity and there's a lot of promise but also complexity, which again, leads to the necessity to have all of them in the room and discuss where we are going.

What do you think the future looks like in the space?

It is relatively safe to say that the movement goes towards more targeted therapy in hematologic malignancies and immunotherapies, which also includes reduction of high doses of chemotherapy. The future will lead to combination therapies or sequencing of therapies, where chemotherapy will likely more and more be eliminated and replaced by immunotherapies or targeted therapies.

That has many advantages. Without knowing at this point whether or not the duration of the remission, or the possibility of cure will be the same, there's a good chance because that's what the immune system is built for to begin with. It is already clear that with replacement of chemotherapy with immunotherapeutic drugs, the side effect profile will come down and has come down significantly. Even if the quality of life is the only factor that improves, that would be a big win.

What are the key takeaways you hope people gain from this meeting?

The key takeaways will be to learn about combinations that are in development that will improve the outcome of patients with hematologic malignancies by reducing the side effect profile, and with that, increasing the quality of life. We don't know for sure what the best time is for the drugs that are targeted at high-risk AML, how to combine them with the standard approaches. Stem cell transplantation will not go away but the timing of the stem cell transplantation in this new era will likely be looked at again and revised so that we can optimize the outcome of the treatments and patient care.