10 min

Cancer Topics - CAR T-cells in Pediatric ALL ASCO Education

    • Medicine

Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org.
 
Transcription:  The purpose of this podcast is to educate and inform. This is not a substitute for medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL.

One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL.

Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later.

Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice.

She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive.

Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy.

He then received a four-week course of the CD3/CD19 BiTE blinatumomab,

Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org.
 
Transcription:  The purpose of this podcast is to educate and inform. This is not a substitute for medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL.

One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL.

Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later.

Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice.

She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive.

Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy.

He then received a four-week course of the CD3/CD19 BiTE blinatumomab,

10 min