Impact of CAR T-Cell Therapy on Use of SCT for Hematologic Malignancies

Robert J. Soiffer, MD, the chair of the executive committee for clinical programs, vice chair of the department of medical oncology, chief of the division of hematologic malignancies, and institute physician at Dana-Farber Cancer Institute, discusses the approaches to integrating chimeric antigen receptor (CAR) T-cell therapy into the treatment of hematologic malignancies.

Soiffer says that currently CAR T-cell therapies have not had an impact in myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), due to the difficulty targeting the cancer. CAR T cells may also target healthy hematopoietic stem cells in these patients, causing significant adverse events. One potential solution would be combining CAR T-cell therapy with allogeneic hematopoietic stem cell transplant (SCT) to introduce healthy stem cells that would not be targeted.

In addition, hematologists need to determine how to introduce CAR T-cell therapies in patients with non-Hodgkin lymphoma, according to Soiffer, now that they have been approved for large B-cell lymphomas. Based on the trials, patients who are refractory to primary therapy or have an early relapse within 12 months after therapy should be considered as candidates for CAR T-cell therapy as an alternative to cytoreductive chemotherapy followed by autologous SCT.

TRANSCRIPTION:

0:08 | At the present time, in terms of AML and MDS for which we often do allogeneic transplants, CAR T cells have not yet had an impact. I think there are some challenges with CAR T-cell therapy for AML as to determining what the correct target is for AML. There are also challenges in terms of concern for the consequences of a successful CAR T-cell eradication in leukemia because those CAR T cells may actually target normal hematopoietic stem cells and result in prolonged aplasia and low blood counts. It may be that we're going to have to combine—if we will get to the point where we have a successful CAR T cells for AML—we may have to combine that with allogeneic transplant. Integrate it so that we have a sequential approach where we either first eliminate the tumor with CAR T cells and then go on to perform an allogeneic transplant or conceivably vice versa in the opposite direction.

So, that's the future. For the present, I think that we will need to decide as a community, how we're going to integrate CAR T-cell therapy in for patients with non-Hodgkin lymphoma, high-risk large cell lymphoma specifically, who are either primary refractory, or who have had an early relapse after their initial therapy.