Exploring Transplants Prior to CAR T-Cell Therapy in Hematologic Malignancies

Robert J. Soiffer, MD, discusses the use of stem cell transplant in treating hematologic malignancies prior to the availability of chimeric antigen receptor T-cell products.

Robert J. Soiffer, MD, 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, as well as the Worthington and Margaret Collette Professor of Medicine in the field of hematologic oncology, Harvard Medical School, discusses the use of stem cell transplant in treating hematologic malignancies prior to the availability of chimeric antigen receptor (CAR) T-cell products.

Prior to the development of CAR T-cell therapies, stem cell and allogeneic transplants have been the 2 main approaches for treating patients with hematologic malignancies, according to Soiffer. Transplant has been the standard of care for many hematologic malignancies and has been used for over 40 years.

Stem cell transplants are typically performed in patients with non-Hodgkin lymphoma and multiple myeloma, while allogeneic transplants typically are for patients with acute myelogenous leukemia, myelodysplastic syndrome, myelofibrosis, and more.

However, with developments focused on evolving CAR T-cell therapies, the main treatment approach for this patient population may change.

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0:08 | We've been doing transplantation now for close to 40 years. There are 2 types of transplants. There is autologous transplantation which is someone who uses their own stem cells. Stem cells are taken out prior to the transplant, and they're usually frozen. And then we give the patient high doses of chemotherapy or chemotherapy and radiation and then infuse those stem cells back, like sort of a stem cell rescue. These transplants are typically done for diseases like non-Hodgkin lymphoma and multiple myeloma.

0:44 | In terms of allogeneic transplant where we use someone else's cells, usually for a disorder where the bone marrow is heavily involved with a malignancy, that includes acute myelogenous leukemia and other stem cell disorders like myelodysplastic syndrome, and myelofibrosis.

1:07 | The allogeneic transplants are more toxic than autologous transplants, they run the risk of causing graft versus host disease. But they play an important role in the treatment of patients with blood cancers. They have become part of standard of care for patients with hematologic malignancies over the past 3 decades, and their use has increased year after year. They've increased it to some extent, because we are now able to offer allogeneic transplant to patients who are quite older, up to their late 70s. Individuals who are relatively fit in the late 70s can undergo successful transplant. That’s opened opportunities which weren't open many years ago.

1:53 | In addition, in terms of allogeneic transplant when we’re using a donor. When I started 40 years ago, we were limited to young patients who had siblings, brothers and sisters, who are identical. Over my career, we've been able to extend that to use alternative sources of stem cells, either unrelated donor stem cells as volunteers from around the world, who are selflessly willing to donate their metabolic stem cells to a stranger, or haploidentical transplant which is half-match transplants, using brothers or sisters, parents, or children. That’s due to some of the great work that’s been piloted out of Johns Hopkins and other institutions.