Harnessing the Immune System for Cancer Treatment with Dr. Kindwall-Keller

Title: Harnessing the Immune System for Cancer Treatment

Speaker: Tamila L Kindwall-Keller, DO, Assistant Professor of Medicine at UVA and the Associate Clinical Director of the Stem Cell Transplant Program.

Abstract: Chimeric Antigen Receptor T (CAR-T) cell therapy has been shown to have anti-tumor activity in pediatric acute lymphoblastic leukemia (ALL), diffuse large b-cell non-Hodgkin’s lymphoma, mantle cell non-Hodgkin’s lymphoma, multiple myeloma and chronic lymphocytic leukemia. Three commercial CD-19 CAR-T cell therapies tisagenlecleucel, axicabtagene ciloleucel and brexucabtagene autoleucel are currently available in the United States, with many more on the horizon. Cytokine release syndrome, a common side effect of CAR-T therapy, results from supraphysiologic cytokine levels that can occur within hours and up to 30 days after the administration of therapy. Fever, hypotension, tachycardia, tachypnea, hypoalbuminemia, coagulopathy and in rare cases multi-organ failure has been seen in CRS. The clinical presentation of CRS may vary depending on which CAR-T cell therapy is given. Neurotoxicity, known as immune-effector cell associated neurotoxicity (ICANS), can occur with CAR-T therapy. Symptoms of ICANS may include tremor, dysgraphia, difficulty with expressive speech, apraxia, fatigue, and impaired attention. Both CRS and ICANS can range from mild to severe, requiring intensive care unit stays and even death. Understanding how these agents work and the underlying pathophysiologic processes at work will help us develop treatments for the devastating side effects.

About the speaker: Dr. Kindwall-Keller's clinical interests include acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, acute myeloid leukemia, Hodgkin lymphoma, multiple myeloma, myelodysplastic syndrome,  non-Hodgkin lymphoma, and hematopoietic stem cell transplantation (bone marrow transplant). Dr. Kindwall-Keller’s primary research focus is centered around the clinical application of alternative graft sources for stem cell transplant used in the treatment of hematologic malignancies, psychosocial assessment and quality of life measures for stem cell transplant patients, and developing new therapeutic drugs for the treatment of multiple myeloma before and after stem cell transplantation. She has worked to develop stem cell transplant and therapeutic drug trials and has been the medical monitor for several national cooperative group stem cell transplant trials.