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Accreditation/ Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

These activites are not approved for AMA PRA Category 1 Credit™.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.

Advances in™ Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap



1 of 3
PER Pulse Recap

The online CME activity, Advances in™ Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies, features clinical data summaries and video interviews with Daniel DeAngelo, MD, PhD, and Jae Park, MD, centered around the treatment of hematologic malignancies with chimeric antigen receptor (CAR)-modified T cells. Throughout the interviews, the faculty discuss new data and provide perspectives on how the technology and application of CAR T cells continue to evolve.

This first of 3 PER Pulse™ Recaps focuses on the technology of CAR T cells and their distinct therapeutic properties.

  • What CAR T cells are: CAR T cells are T cells from the patient that are modified or re-engineered to express a CAR, which is a kind of artificial T-cell receptor. The CAR consists of a binding domain, for localization to the cancer cell, that is fused to a signaling domain to stimulate the T cell.
  • How CAR T cells are different from other therapies: Compared to most anticancer agents, CAR T cells have the potential, as a living drug, to provide long-term immunity, which is dependent on their ability to persist. Compared with immune checkpoint inhibitors, CAR T cells are intended to provide immediate and specific activity against tumor cells bearing the antigen to which the CAR is aimed.
  • Overview of the treatment process: A patient’s T cells are harvested through apheresis, transfected to express the CAR, expanded, and reinfused to the patient.
  • Current and future applications: Current studies have focused on patients with relapsed/refractory hematologic malignancies, particularly acute lymphoblastic leukemia. However, clinical trials have rapidly expanded to other hematologic malignancies and solid tumors.
  • Visit
www.gotoper.com to access Advances in Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies and additional PER Pulse™ Recap commentaries on this activity.

 



2 of 3
PER Pulse™ Recap

The online CME activity, Advances in™ Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies, features clinical data summaries and video interviews with Daniel DeAngelo, MD, PhD, and Jae Park, MD, centered around the treatment of hematologic malignancies with chimeric antigen receptor (CAR)-modified T cells. Throughout the interviews, the faculty discuss new data and provide perspectives on how the technology and application of CAR T cells continue to evolve.

This second of 3 PER Pulse™ Recaps focuses on clinical experience with CAR T cells in patients with hematologic malignancies.

  • Acute lymphoblastic leukemia (ALL): Whereas conventional chemotherapy is associated with complete response (CR) rates of only 20% to 40% in patients with relapsed/refractory ALL, CAR T cells have yielded CR rates of up to 90%. The recent phase 2 ELIANA trial showed a CR rate of 68%, with an overall remission rate of 82% and minimal residual disease negativity in 82% of patients.
  • Diffuse large B-cell lymphoma (DLBCL): In patients with relapsed/refractory DLBCL, salvage therapy yields low rates of CR, as low as 2% after multiple lines of therapy. Recent trials with CAR T cells have demonstrated CR rates of approximately 50% to 60%; in the DLBCL cohort of the multicenter ZUMA-1 trial, 47% of the patients achieved a CR.
  • Chronic lymphocytic leukemia (CLL): While the development of targeted agents in CLL has improved outcome even for patients with high-risk disease, patients failing these agents have few options and a poor outcome. In patients with relapsed/refractory CLL, including patients with ibrutinib-refractory disease, CR rates of 20% to 25% have been observed with CAR-T-cell therapy.

Visit www.gotoper.com to access Advances in Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies and additional PER Pulse™ Recap commentaries on this activity.


3 of 3
PER Pulse™ Recap

The online CME activity, Advances in™ Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies, features clinical data summaries and video interviews with Daniel DeAngelo, MD, PhD, and Jae Park, MD, centered around the treatment of hematologic malignancies with chimeric antigen receptor (CAR)-modified T cells. Throughout the interviews, the faculty discuss new data and provide perspectives on how the technology and application of CAR T cells continue to evolve.

This third of 3 PER Pulse™ Recaps focuses on challenges in improving CAR T-cell therapy.

  • Safety: A major challenge with an immune-based therapy, such as CAR T cells is immune-related toxicities. With CAR T cells, cytokine release syndrome (CRS) and neurotoxicity are the 2 main adverse events; both can become severe and fatal if not managed. The degree of CRS is thought to relate to disease burden and disease type, with higher rates of CRS observed in patients with acute lymphoblastic leukemia. The main interventions include blockade of interleukin-6 signaling and the use of steroids. Early intervention algorithms are also being investigated to reduce the incidence of severe CRS. The mechanism of neurotoxicity is unclear, however, and an optimal management strategy is yet to be determined.
  • Persistence: While CAR T cells can generate high rates of complete response, the durability of the response can be shortened due to loss of the tumor antigen and immune clearance of the CAR T cells. CAR T cells with specificity for different tumor antigens are being explored to address the loss of antigen. Next-generation CARs are being explored to improve immune persistence, including using humanized (rather than murine) genes for the extracellular portion, and with so-called armored CAR T cells that secrete cytokines to create a favorable microenvironment.

Visit www.gotoper.com to access Advances in Immunotherapy: The Expanding Potential of CAR T-Cell Therapy for Hematologic Malignancies and additional PER Pulse™ Recap commentaries on this activity.






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