Guenther Koehne, MD, PhD, is a pioneer in allogeneic stem cell transplantation and immunotherapies. He is course 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.

Guenther Koehne, MD, PhD

New therapies for hematologic malignancies have created a greater number of viable options for providers and patients, particularly for patients who have relapsed. Today’s armament includes chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies, immunotherapeutic approaches, antibody-drug conjugates, chemotherapy-free inductions, and multidrug combinations. The excitement surrounding these advances and improved outcomes in very difficult-to-treat diseases is palpable. Yet the complexities of these therapies also bring their own complications. 

In order to build upon the headway made in the management of leukemia, lymphoma, multiple myeloma, and stem cell transplantation, clinicians must leave their research silos to share information and brainstorm with each other. That’s exactly what some of the nation’s top physicianscientists did at the 3rd Annual Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies, held April 8-9, 2022, in Florida. 

For example, Siddhartha Mukherjee, MD, of Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York, spoke on novel approaches of CAR T-cell therapies for acute myeloid leukemia (AML), specifically the first-in-human clinical trial Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ and AML (NCT04849910). The Miami Cancer Institute is currently enrolling patients in the multisite trial. 

Mukherjee joined Richard Stone, MD, and Robert J. Soiffer, MD, both of Dana-Farber Cancer Institute in Boston, Massachusetts, for a fast-paced roundtable discussion on the newest treatments for AML. 

Among the topics reviewed were the role of the intestinal microbiome in hematopoietic stem cell transplantation and the influence of the gut’s microbial composition on graft-vs-host disease, the first-in-human clinical trials using CRISPR/Cas9 technology to silence the expression of CD33 on stem cells and infuse the CD33-negative stem cells, and the shift from triplet combination therapies to 4-drug regimens in multiple myeloma. The group also discussed B-cell maturation antigen–directed therapies for multiple myeloma, treatment approaches in diffuse large B-cell lymphoma, and improving outcomes in T-cell acute lymphoblastic leukemia (ALL). 

In another presentation, Marcel R. M. van den Brink, MD, PhD, the Alan N. Houghton Chair and head of the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center in New York, New York, referred to diet having a role in preventing potentially lethal graft-vs-host disease. His work has explored the use of antibiotics to destroy specific gut flora and the introduction of fecal transplants to boost beneficial bacteria. A study published in the 

 detailed the results of 8767 fecal samples from patients undergoing allogeneic hematopoietic cell transplantation at 4 centers. Patients with the highest diversity of intestinal microbiota had the lowest risk of death (HR, 0.71; 95% CI, 0.55-0.92).

In his presentation on treatment updates for ALL, Hagop M. Kantarjian, MD, a professor and Samsung Distinguished Leukemia Chair in Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, shared the success of his research in chemotherapyfree induction and reduced toxicity regimens,

 particularly for older patients with ALL, a group whose complex disease has resulted in lower survival rates. The work holds considerable promise, prompting talk of the possibility that the majority of these patients will no longer require allogeneic transplants. 

There is great hope for continued improved outcomes as these new techniques and strategies evolve; conditioning regimens, induction timing and dosing levels are adjusted; and different drug combinations are introduced. Through intimate meetings such as the summit, which provide participants the opportunity to ask questions and talk one-on-one and in small group settings, the cancer care environment will continue to evolve. 

Watch for more information on the Miami Cancer Institute’s 4th Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies. 

1. Peled JU, Gomes ALC, Devlin SM, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. 

2020;382(9):822-834. doi:10.1056/NEJMoa1900623 

2. Rausch CR, Jabbour EJ, Kantarjian HM, Kadia TM. Optimizing the use of the hyperCVAD regimen: clinical vignettes and practical management. 

2020;126(6):1152-1160. doi:10.1002/cncr.32606

Articles

The excitement surrounding advances and improved outcomes in very difficult-to-treat diseases is palpable. Yet the complexities of these therapies also bring their own complications. 

Next-Generation Treatments for Blood Cancers: Improved Outcomes in the Forecast

New therapies for hematologic malignancies have created a greater number of viable options for providers and patients, particularly for patients who have relapsed. Today’s armament includes chimeric antigen receptor (CAR) T-cells, bispecific antibodies and immunotherapeutic approaches, antibody conjugates, chemotherapy-free inductions and multi-drug combinations. The excitement surrounding these advances is palpable, as we are seeing improved outcomes in these very difficult-to-treat diseases. Yet the complexities of these therapies also bring their own complications.

In order to build upon our headway in the treatment of leukemia, lymphoma, multiple myeloma and stem cell transplantation, we must leave our research silos to share information and brainstorm with each other. That’s exactly what some of the nation’s top physician-scientists in the field did at Miami Cancer Institute’s Third Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies, held April 8-9, 2022.

Among the topics were the role of the intestinal microbiome in hematopoietic stem cell transplantation and the influence of the gut’s microbial composition on graft versus host disease; the first in-human clinical trials using CRISPR/Cas9 technology to silence the expression of CD33 on stem cells and infuse the CD33-negative stem cells; and the shift from triplet combination therapies to four-drug regimens in multiple myeloma. The group also discussed BCMA-directed therapies for multiple myeloma, treatment approaches in diffuse large B-cell lymphoma and improving outcomes in T-ALL.

For example, Marcel van den Brink, M.D., Ph.D., of Memorial Sloan Kettering, referred to diet as a drug capable of preventing potentially lethal graft versus host disease. His work has explored the use of antibiotics to destroy specific gut flora and the introduction of fecal transplants to boost beneficial bacteria. A study published in the NEJM detailed the results of 8,767 fecal samples from patients undergoing allogeneic hematopoietic-cell transplantation at four centers. Patients with the highest diversity of intestinal microbiota had the lowest risk of death.

Hagop Kantarjian, M.D., from MD Anderson Cancer Center, shared the success of his research in chemotherapy-free induction and reduced toxicity regimens

, particularly for older patients with acute lymphoblastic leukemia, a group whose complex disease has resulted in lower survival rates. The work holds considerable promise and brought about further talk of the possibility that the majority of these patients will no longer require allogeneic transplants.

Siddhartha Mukherjee, M.D., of Columbia University’s Herbert Irving Comprehensive Cancer Center, spoke on novel approaches of CAR T-cell therapies for acute myeloid leukemia, specifically the first-in-human clinical trial, “Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ and AML.”

 Miami Cancer Institute is currently enrolling patients in the multi-site trial.

In addition, Dr. Mukherjee joined Richard Stone, M.D., and Robert Soiffer, M.D., both of Dana-Farber Cancer Institute, for a fast-paced roundtable discussion on the newest treatments for AML.

As these new techniques evolve and we adjust conditioning regimens, induction timing and dosing levels, as well as introducing different drug combinations, we are very hopeful that we will continue to see improved outcomes. Through intimate meetings such as the Summit, which provide participants with the opportunity to ask questions and talk one-on-one and in small group settings with each other, we will change the cancer care environment. Watch for more information soon on the Fourth Annual Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies.

1. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. Accessed April 12, 2022. https://www.nejm.org/doi/full/10.1056/NEJMoa1900623

2. Optimizing the use of the hyperCVAD regimen: Clinical vignettes and practical management. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.32606

3. Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ and AML. https://clinicaltrials.gov/ct2/show/NCT04849910

As these new techniques evolve and we adjust conditioning regimens, induction timing and dosing levels, as well as introducing different drug combinations, we are very hopeful that we will continue to see improved outcomes for hematologic malignancies, says Guenther Koehne, MD, PhD.

Next Generation Treatments for Blood Cancers: Improved Outcomes in the Forecast

Guenther Koehne, MD, PhD, deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, and director of the Summit of the Americas on Immunotherapies for Hematologic Malignancies discusses the exciting presentations going on at the 3rd Annual Meeting.

At the summit, multiple speakers will cover updates in approaches to treating lymphomas, acute lymphoblastic leukemia, and multiple myeloma. There will also be important discussions around chimeric antigen receptor (CAR) T-cell therapy and allogeneic stem cell transplantation.

 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 of new 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. Now, he will give us a keynote address and update on the future of CAR T cell therapies.

Now, this raises also 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 Soiffer, who will pick up on this topic, which I think is critical to address.

Videos

Guenther Koehne, MD, PhD,  discusses the exciting presentations going on at the 3rd  Summit of the Americas on Immunotherapies for Hematologic Malignancies. 

Excitement Around Immunotherapies for Hematologic Malignancies

Harnessing the ability of the body’s own immune system, particularly with the use of chimeric antigen receptor (CAR) T cells, has already made a significant impact on the survival of patients with some hematologic malignancies. Perhaps the most exciting news, however, is that what we have learned in the infancy of our work with CAR T-cell therapy (which first received FDA approval in 2017), along with new information gleaned from ongoing research and clinical trials, is helping us develop next-generation immunotherapy treatments that are specifically tailored to the individual. In addition, it is expanding the types of cancers and patients that can be treated with CAR T cells.

At Miami Cancer Institute’s Second Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies, held May 14, 2021, some of the nation’s top experts shared the latest advances. For example, Robert Soiffer, MD, from Dana Farber Cancer Institute, reviewed real-world results published in the last year that show CR rates for patients with diffuse large B-cell lymphoma ranging from 40 to 64 percent and ORR rates ranging from 59 to 82 percent (from Jacobson, Nastoupil, Pasquini and others).

As we adjust conditioning regimens, induction timing and dosing levels, we continue to have many questions, but are greatly encouraged. Is it possible that one day in the future, we will use CAR T cells instead of transplantation or as a bridge to transplantation? Will CAR T cells or other CAR cells replace chemotherapy for some? Time will tell.

Paul Lin, MD, of MD Anderson Cancer Center, spoke on CAR cells being introduced into other immune effector cells. And he showed that CAR-NK (natural killer) cells can be used to treat DLBCL, and that by adding a checkpoint inhibitor, a booster effect is felt.

 While scientists are looking at the benefits of many cells that bolster the immune system, research into CAR-NK cells is advancing quickly and it may be that CAR-NK, with lower toxicity and off-the-shelf availability, will eventually provide an additional CAR immunotherapy approach.

At the Herbert Wertheim College of Medicine at Florida International University, Robert Sackstein, MD, PhD, has shown that inducing expression of E-selectin ligand on CAR T-cells can improve the acceleration of the genetically altered cells directly to the tumor site.

 Among the benefits are the ability to induce a complete remission using fewer cells, and thereby reducing toxicities.

The issue of toxicity, particularly among older and more frail patients, is an interest of Wendy Stock, MD, of the University of Chicago. She reported that her work in using immunotherapy drugs rather than standard chemotherapy in older adults with acute lymphoblastic leukemia is moving immune targeting to the frontline.

While the volume and variety of information coming from current studies seems overwhelming, it is what is changing the cancer care environment today. Many of these studies are aimed at patients with very complex and relapsing disease. These advances, that also include a better understanding of how biomarkers relate to treatment response, are leading us to significant improvements in patient care.

1. Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells. Accessed May 13, 2021. https://bit.ly/3oV251u 

2. Glycoengineering of chimeric antigen receptor (CAR) T-cells to enforce E-selectin binding. 

3. Patel AA, Heng J, Dworkin E, et al. Expanding use of a modified pediatric intensive regimen for acute lymphoblastic leukemia (ALL) into an older adult population: feasibility and efficacy results. 

While the volume and variety of information coming from current studies seems overwhelming, it is what is changing the cancer care environment today.

Guenther Koehne, MD, PhD | Authors

Articles

Next-Generation Treatments for Blood Cancers: Improved Outcomes in the Forecast

Next Generation Treatments for Blood Cancers: Improved Outcomes in the Forecast

Excitement Around Immunotherapies for Hematologic Malignancies

CAR T Cells and Beyond: An Exciting Future for Immunotherapy