An adage of evidence-based medicine is that the management of any disease requires skilled, collaborative and experienced specialists who have treated a substantial population of patients over a long period time.
Penn Medicine’s Abramson Cancer Center (ACC) and its dedicated CAR-T research and treatment program is no exception — building the foundation for modern cancer immunotherapy research over the course of the last 30 years.
The Abramson Cancer Center has established a dedicated, unified team that defined and advanced the power of CAR-T cell therapy in B-cell malignancies while treating more than 400 patients.
Our research and clinical team’s efforts were exemplified when the FDA approved Kymriah™ (tisagenlecleucel) in 2017 ─ a CAR-T therapy initially developed at Penn, for patients up to 25 years of age with relapsed or refractory B-cell ALL. Recently, on May 1, 2018, the FDA also approved Kymriah for the treatment of patients with diffuse large B cell lymphoma (DLBCL) — a highly aggressive and difficult-to-treat non-Hodgkin lymphoma.
Managing the unique challenges presented in CAR-T
As every medical professional knows, the benefits of every therapy are attended by certain risks. For CAR-T, the most prominent and severe of these risks is cytokine-release syndrome (CRS), an on-target side effect first recognized and effectively managed at the Abramson Cancer Center and the Children’s Hospital of Philadelphia.
CRS was encountered early in the process of developing CAR-T therapy by Carl June, MD, and his colleagues, who subsequently identified the proinflammatory cytokine IL6 as a central mediator of CRS toxicity. A known cause of rheumatoid arthritis and other autoimmune diseases, IL6 is effectively managed by the anti-IL6 receptor antibody tocilizumab. With the demonstration that tocilizumab rapidly reverses the manifestations of CRS in most CAR-T patients, Dr. June and his team were responsible not only for a primary cancer therapy, but for the amelioration of its principal adverse effect.
Linked to the proliferation of cytokines (inflammatory proteins that play a role in immune activation) that occurs soon after CAR-T cells are infused back into a patient during therapy, CRS manifests as a low grade fever that escalates over time, and can become dangerously high. For CAR-T patients, the fever is considered a good sign that the therapy is killing tumor cells.
At Penn Medicine, our researchers and clinical team continue to drive progress and improve our understanding of CRS through the developments of predictive models and detailed treatment algorithms to enhance patients’ safety and outcomes. We continue to collaborate with referring oncologists throughout their patient’s treatment, and post-discharge, to manage the complexities of the therapy and ensure that patients receives the best care and outcomes.
Is your patient a candidate for CAR-T cell therapy?
If you have a patient who may be appropriate for CAR-T cell therapy, we encourage you to consult with us through one of the following channels:
Due to the complexities of CAR-T, our team will collaborate with you throughout the treatment process and post discharge to ensure your patient receives the best care and outcome.
Clinical trials
Referring physicians may also be interested in the open CAR-T clinical trials in blood cancers and solid tumors at the Abramson Cancer Center:
Additional CAR-T resources at Penn