Maintenance Therapies Needed to Prevent Relapse After Transplant

Robert J. Soiffer, MD

Oncologists are on the cusp of helping to prevent relapse patients with cancer after transplant with the use of maintenance therapies. For patients with hematologic malignancies like acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), one type of therapy making headway is tyrosine kinase inhibition.

Prior to transplant, clinicians also utilize immunotherapy conjugates for their patients. Now, these agents are starting to be assessed in the post-transplant setting.

“Years ago, when I started in transplantation, we viewed a transplant as the last gasp [or] what we do at the end of a patient's treatment course to try to save them and try to cure them of their malignancy…These days, however, transplant is much better tolerated. We have the opportunity to combine transplantation with a variety of agents, both chemotherapy agents, immunotherapy agents, cellular therapy approaches, to actually treat relapse, or even better, prevent relapse using these agents in a maintenance setting,” Robert J. Soiffer, MD, said in an interview with Targeted Oncology^TM.

According to Soiffer, the chair, Executive Committee for Clinical Programs, vice chair, Department of Medical Oncology, chief, Division of Hematologic Malignancies and institute physician at Dana-Farber Cancer Institute, and a presentation he gave at the 4th Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies, researchers must now focus their efforts on maintenance therapies and the prevention of relapse.

By further understanding which patients are most likely to relapse, which therapies to use, and how to provide patients with those treatments, patients with many hematologic malignancies, including leukemia, lymphoma, myeloma, etc., will have improved outcomes and less of a chance for relapse after transplant.

In the interview, Soiffer discussed relapse after transplant for patients with cancer and what is important to note moving forward with research.

Targeted Oncology: Can you discuss the current role of transplantation? Why is it important to discuss relapse after transplant for patients with cancer?

Soiffer: Oftentimes, when we consent patients for transplant, we concentrate on complications, like organ toxicity, infection, graft-vs-host disease, but we often don't address the elephant in the room, which is relapse after transplant, which is, of course, the real reason we're doing the transplant in the first place. Indeed, in patients who are beyond day 100 of relapse represents the primary reason for cause of death. We really have to make a concerted effort to address the issue of relapse.

Years ago, when I started in transplantation, we viewed a transplant as the last gasp [or] what we do at the end of a patient's treatment course to try to save them and try to cure them of their malignancy. It usually wasn't much to do after transplant or in conjunction with transplant because transplant itself was so toxic. These days, however, transplant is much better tolerated. We have the opportunity to combine transplantation with a variety of agents, both chemotherapy agents, immunotherapy agents, cellular therapy approaches, to actually treat relapse, or even better, prevent relapse using these agents in a maintenance setting.

Are there any ongoing trials or recent research that has caught your eye in this space?

There are a number, and they largely revolve around maintenance efforts to try to prevent patients from relapsing. These include the use of targeted agents and tyrosine kinase inhibitors that are now becoming much more popular and have become a standard of care in the treatment of many patients with AML and ALL, as well as immunotherapy conjugates that are used to treat patients prior to transplant. They're now being looked at in the post-transplant setting as maintenance.

Can you discuss the role of stem-cell transplant for hematological malignancies prior to the availability of CAR T-cell products?

Prior to the advent of CAR T-cell or immune effector cell approaches allogeneic transplant or autologous transplant represented the main cellular therapy for patients with blood cancers. They could be employed in a variety of circumstances, either in the autologous transplant setting in patients with non-Hodgkin lymphoma or Hodgkin lymphoma, and multiple myeloma, or the allogeneic setting for these very same diseases or those individuals with acute leukemia, MDS, or myelofibrosis.

They were used quite frequently in many circumstances. We didn't use them in all patients, as there were patients who were considered good risk patients by their biologic characteristics or their clinical characteristics. We wouldn't expose those patients to transplant because of the potential toxicity of transplant, hoping that standard therapy would be sufficient to cure them. Those individuals who were high-risk patients by their clinical or genomic characterization or those individuals who had not responded to primary therapy with those individuals are those individuals who we employ hematopoietic stem cell transplant for.

What unmet needs still exist regarding transplants?

We have been doing transplants for 50-60 years at this point. I've been doing it for just about 40 years, and we've made some good progress, but we have a long way to go. Transplant is still too toxic. There is a mortality associated with it, particularly with allogeneic transplants. Even if we've improved substantially, we want to have a therapy that we can offer patients that doesn't put their life at jeopardy. We need to continue to improve the safety of transplant. As I said, we've come a long way there.

The topic of my talk from Miami discussed relapse after transplant. There we have to cooperate. Those who work with allogeneic transplants have to collaborate with disease focused colleagues, whether it be leukemia, lymphoma, myeloma, or other diseases, to work together to try to bring down that risk of relapse, first by getting patients more ready for transplant and at a better minimal disease state going into transplant, and then working on ways to continue that therapy after transplant to try to suppress the risk of relapse.

What is important to note about relapse after transplant?

The real focus needs to be on maintenance therapies and the prevention of relapse. We must understand who is likely to relapse, how to deploy those therapies, and work together with our disease experts in leukemia, lymphoma, myeloma, and more, to combine the best of non-transplant therapies with transplants.