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The Genome
CMECNE

CAR T-Cell Therapy: FDA Approves ‘Living Drugs’ for Cancer Treatment in Children and Adults

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Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Explain the fundamental technology underlying CAR T-cell construction
2. Discuss how CAR T-cell therapy is being used in oncology

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The PIM planners and others have nothing to disclose. The OBG Project planners and others have nothing to disclose.

Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from 12/31/2017 through 1/25/2023, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.

Read Disclaimer & Fine Print

WHAT IS IT?

  • ‘CAR’ (chimeric antigen receptor) refers to the synthetic receptors that are genetically engineered and integrated into the T-cell surface
  • CAR T-cell therapy is a type of adoptive cell transfer (ACT) where a patient’s cells are removed, genetically engineered to attack her cancer cells and then returned back to the patient

HOW ARE CAR T-CELLS MADE AND USED TO ATTACK CANCER CELLS?

  • The genetically engineered CAR is not an antibody found in nature but rather is a synthetic construct that is made up of various fragments and domains
    • T-cells from a patient with cancer are engineered to produce these CAR T-cells, outfitted with synthetic antibodies specific to the target cancer cell antigen, which are then infused back into the patient
    • Scientists choose domains that will maximize recognition of the target antigen on the tumor cell
  • Domains within the cell are also important and designed to affect cell function
  • Continuing research has led to improvements in
    • Expansion (ability of CAR T-cells to multiply after infusion into the patient)
    • Persistence (survival after infusion into the patient)
    • Production time (from weeks to days)

FDA APPROVAL 2017:

Pediatric Oncology

  • FDA (August 2017) approved the first CAR T-cell therapy, tisagenlecleucel, for children with acute lymphoblastic leukemia (ALL) who have relapsed at least twice or who have not responded to standard therapy
    • The synthetic antibodies target the CD19 antigen found only on B-cells
    • The CAR T-cells undergo expansion in the laboratory, are infused back into the patient following lymphodepletion and then will undergo expansion again
    • Many of the children in the tisagenlecleucel trials have had complete long lasting remissions
      • Previously, no known treatment available
    • The FDA granted tisagenlecleucel Priority Review and Breakthrough Therapy designations

Adult Oncology

  • FDA (October 2017) approved the first drug for adults, axicabtagene ciloleucel, for the treatment of an aggressive type of non-Hodgkin lymphoma
    • This CAR T-cell therapy targets CD19 cells and is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
  • Individuals with DLBCL will go into remission after treatment but approximately a third either don’t respond or relapse and on average will survive only 6 months
  • In a drug trial that included 101 patients, 36% went in to remission and in 82%, the tumor shrank by ≥ 50%
  • Known risks were seen in the trial, including brain toxicity

Examples of ACT: TCR T-cells and CAR T-cells (tap to enlarge)

NCI-CART-cells

Credit: National Cancer Institute

KEY POINTS:

  • Other examples of ACT beyond CAR T
    • Tumor-Infiltrating Lymphocytes (TILs): Immune cells that can penetrate tissues around the tumor based on cancer mutation recognition
      • Currently being studied in colorectal and liver cancer
    • T-cell Receptors (TCRs): As opposed to CAR T approach, TCRs use naturally receptors that recognize antigens within tumor cells
      • Currently being studied in melanoma and sarcoma
  • CAR T-cell therapy side effects include
    • Cytokine-release syndrome (CRS) that results from rapid and massive release of cytokines into the bloodstream resulting in fevers and hypotension
      • Indicates T-cells are working
      • CRS manageable with supportive therapies
    • B-cell aplasia, where B-cells, including normal cells, are killed off by the CAR T-cell therapy
      • Treatment includes immunoglobin therapy to fight dangerous infection
    • Cerebral edema noted in some trials but not others
    • Neurotoxicity (confusion or seizure-like activity) which is short lived and reversible

LEARN MORE – PRIMARY SOURCES:

FDA News Release:  FDA approval brings first gene therapy to the United States 

CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers

Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment

Driving CAR T-cells forward

FDA Approved Drugs: YESCARTA (axicabtagene ciloleucel)

FDA Approved Drugs: KYMRIAH (tisagenlecleucel)

Take a post-test and get CME credits

TAKE THE POST TEST

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CRISPR Nobel Prize Technology: “A tool for rewriting the code of life”
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Computer System Requirements

OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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