Accreditation/Credit Designation

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

Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians’ Education Resource®, LLC, is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours.

Acknowledgment of Commercial Support

This activity is supported by educational grants from Celgene Corporation and Gilead Sciences, Inc.

Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community


Release Date: June 21, 2019
Expiration Date: June 21, 2020
Media: Internet - based

Activity Overview

This Medical Crossfire® program, featuring chimeric antigen receptor T-cell (CAR T) experts Jae Park, MD, and Krishna Komanduri, MD, as well as medical oncologists Alvaro J. Alencar, MD, and S. Peter Wu, MD, will help facilitate coordination between oncologists in the community and oncologists in specialized treatment centers. Expert panelists discuss some of the latest developments in the field of CAR T therapy, with a focus on pivotal clinical trial data and key trials in progress. Methods of patient assessment, considerations in candidacy for CAR T therapy, and a recognition of the best practices for management of potential adverse events and follow-up are important activities in this program.

CME Activity Table of Contents

  • Module 1: Introduction
  • Module 2: CAR T Basics for the Practicing Community Oncologist—What You Need to Know
  • Module 3: Medical Crossfire®: CAR T Therapy Basics
  • Module 4: The Process of Patient Selection and Referral With CAR T Therapy
  • Module 5: Patient Follow-up and Adverse Event Management With CAR T Therapy
  • Module 6: Medical Crossfire®: Adverse Event Management and Conquering Barriers to Adoption of CAR T Therapies
  • Module 7: Conclusions

Acknowledgement of Commercial Support

This activity is supported by educational grants from Celgene Corporation and Gilead Sciences, Inc.

Instructions for This Activity and Receiving Credit

  • You will need to log in to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review audio files/content until you finish the presentation.
  • At the end of the activity, educational content/audio files will be available for your reference.
  • In order to receive a CME/CE certificate, you must complete the activity.
  • Complete the Posttest and pass with a score of 70% or higher, complete the Evaluation, and then click on “Request for Credit.” You may immediately download a CME/CE certificate upon completion of these steps.


Target Audience

This educational program is directed toward oncologists and hematologists interested in the treatment and management of lymphoid malignancies with CAR T therapies. Nurse practitioners, physician assistants, nurses, and other healthcare professionals involved in the treatment and management of patients with lymphoid malignancies will be invited to participate.

Learning Objectives

Upon successful completion of this educational program, you should be better prepared to:

  • Realize the unique mechanistic characteristics of CAR T therapies that are important to manufacture and clinical use.
  • Explain clinical trial data with CAR T therapy across hematologic malignancies.
  • Understand pathways for identification of eligible patients, processes for referral to specialized treatment centers, and best practices for follow-up after treatment.
  • Recognize the potential for CAR T treatment toxicities as well as best practices for detection, management, and mitigation of potential toxicities

Faculty, Staff, and Planners’ Disclosures

Chair

Krishna V. Komanduri
Krishna V. Komanduri, MD
Chief, Division of Transplantation and Cellular Therapy
Kalish Family Chair in Stem Cell Transplantation
Professor of Medicine, Microbiology, and Immunology
Sylvester Comprehensive Cancer Center
University of Miami
Miami, FL

Disclosures: Ad Hoc Advisor: Kite/Gilead, Novartis, Adaptimmune, Atara; Consultant: Kite/ Gilead, Celgene, Novartis, Atara, Takeda, Kiadis.

Faculty

Jae H. Park
Jae H. Park, MD
Assistant Attending Physician
Department of Medicine, Leukemia Service
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosures: Consultant: Novartis, Kite Pharma, Allogene.

Alvaro Alencar
Alvaro Alencar, MD
Assistant Professor of Medicine
Member of Lymphoma Program
Medical Director, Hematology/Oncology Inpatient Unit
University of Miami Hospital and Clinics
Sylvester Comprehensive Cancer Center
Miami, FL

Disclosures: Consultant: Advisory Board Kite.

S. Peter Wu
S. Peter Wu, MD
Department of Radiation Oncology
NYU Langone Health
New York, NY

Disclosures: Dr. Wu has no relevant financial relationships with commercial interests to disclose.

The staff of Physicians' Education Resource®, LLC (PER®), have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE activity to disclose all relevant financial relationships with commercial interests. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that create a conflict of interest (COI).

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME/CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME/CE activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician or nurse relative to diagnostic, treatment, or management options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members, and do not reflect those of PER® or any of the companies that provided commercial support for this program.

PER Pulse Recaps

1 of 3
Insight from Jae H. Park, MD–PER Pulse™ Recap:
Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community

Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community is a continuing medical education–certified program. For this program, cochairs Jae H. Park, MD, and Krishna V. Komanduri, MD, were joined by expert faculty Alvaro J. Alencar, MD, and S. Peter Wu, MD, to discuss the implications and clinical applications of noteworthy data, presented at recent international meetings, regarding the treatment of diffuse large B-cell lymphoma (DLBCL), B-cell acute lymphoblastic leukemia (ALL), and other lymphoid malignancies.

This first of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making with regard to appropriate use of chimeric antigen receptor (CAR) T-cell therapy for patients with lymphoid malignancies. Below are some highlights from the activity featuring Dr Park:

  • Lymphoid malignancies originate in B lymphocytes, T lymphocytes, and natural killer cells and include Hodgkin lymphomas and non-Hodgkin lymphomas (NHLs), including DLBCL and follicular lymphoma (FL). Each year, an estimated 666,000 new cases of NHL are diagnosed worldwide. The most common subtype is DLBCL, which accounts for approximately one-third of all cases of NHL.1-4
  • Tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse and adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy including DLBCL not otherwise specified, high grade B-cell lymphoma and DLBCL arising from FL.5
  • Axicabtagene ciloleucel is another CD19-directed, genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from FL.6
  • In the ZUMA-1 phase II trial of 111 patients with relapsed/refractory DLBCL and other refractory NHLs receiving axicabtagene ciloleucel, the best overall response rate was 82% (complete response rate, 54%). At 15.4 months of follow-up, 42% of patients continued to experience treatment response. Adverse events (AEs) of grade 3 or higher severity included neurologic AEs (28% of patients) and cytokine release syndrome (13% of patients).7
  • In the JULIET study of patients with DLBCL or transformed FL that was relapsed or refractory to previous treatments, 115 of 167 enrolled patients had been treated with tisagenlecleucel at the latest follow-up, with a best overall response rate of 52% in 93 patients who were followed at least 3 months. The median duration of response has not been reached, although the probability of relapse-free survival at month 12 is estimated at 64%. Grade 3 to 5 AEs included prolonged cytopenias (34%), cytokine release syndrome (23%), and neurological events (11%).8-10

“There are several different anti-CD19 CAR-T cell products currently available and in development in different disease processes, mainly across B-cell malignancies, such as DLBCL and ALL.”

—Jae H. Park, MD

References

  1. NCI dictionary of cancer terms: B-cell lymphoma. cancer.gov/publications/dictionaries/cancer-terms?cdrid=444967. National Cancer Institute website. Accessed May 21, 2019.
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi: 10.3322/caac.21551.
  3. Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3(4):524-548. doi: 10.1001/jamaoncol.2016.5688.
  4. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780-2795. doi: 10.1200/JCO.1998.16.8.2780.
  5. Tisagenlecleucel [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2018.
  6. Axicabtagene ciloleucel [package insert]. Santa Monica, CA: Kite Pharma, Inc; 2019.
  7. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.
  8. Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56. doi: 10.1056/NEJMoa1804980.
  9. Borchmann P, Tam CS, Jäger U, et al. An updated analysis of JULIET, a global pivotal phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large b-cell lymphoma (DLBCL). Presented at: 2018 European Hematology Association Congress; June 14-17, 2018; Stockholm, Sweden. Abstract S799. library.ehaweb.org/eha/2018/stockholm/214521/peter.borchmann.an.updated.analysis.of.juliet.a.global.pivotal.phase.2.trial.html?f=menu=6*ce_id=1346*ot_id=19046*media=3.
  10. Schuster SJ, Bishop MR, Tam C, et al. Sustained disease control for adult patients with relapsed or refractory diffuse large b-cell lymphoma: an updated analysis of Juliet, a global pivotal phase 2 trial of tisagenlecleucel. Blood. 2018;132:1684. bloodjournal.org/content/132/Suppl_1/1684?sso-checked=true.

2 of 3
Insight from Jae H. Park, MD—PER Pulse™ Recap:
Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community

Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community is a continuing medical education–certified program. For this program, cochairs Jae H. Park, MD, and Krishna V. Komanduri, MD, were joined by expert faculty Alvaro J. Alencar, MD, and S. Peter Wu, MD, to discuss the implications and clinical applications of noteworthy data, presented at recent international meetings, regarding the treatment of diffuse large B-cell lymphoma (DLBCL), B-cell acute lymphoblastic leukemia (ALL), and other lymphoid malignancies.

This second of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making with regard to appropriate use of chimeric antigen receptor (CAR) T-cell therapy for patients with lymphoid malignancies. Below are some highlights from the activity featuring Dr Park:

  • B-cell ALL is the most common leukemia in children, with approximately 6000 new cases expected to be diagnosed in 2019 and an estimated 1500 deaths occurring as a result of the disease.1
  • Currently, the only approved CAR T-cell therapy for B-cell precursor ALL is tisagenlecleucel, which is indicated for use in patients up to 25 years of age with ALL that is refractory or in a second or later relapse.2
  • The indication for tisagenlecleucel in B-cell precursor ALL is based on the ELIANA study, which was conducted in children and adults aged 25 years and younger. In this study, overall remission rate was 81%, including a 62% rate of complete remission and a 19% rate of complete remission with incomplete cytogenetic recovery.3
  • In a study of 19-28z CAR-T therapy at Memorial Sloan Kettering Cancer Center in New York, New York, led by Dr Park, the phase I trial in patients with relapsed B-cell ALL recruited 53 adult patients. Complete remission was observed in 83% of these patients. After 29 months, the median event-free survival was 6.1 months and the median overall survival was 12.9 months. The rate of severe cytokine release syndrome in this study was 36% (14 of 53 patients).4

“There are several different anti-CD19 CAR-T cell products currently available and in development in different disease processes, mainly across B-cell malignancies, such as DLBCL and ALL.”

—Jae H. Park, MD

References

  1. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-448. doi: 10.1056/NEJMoa1709866.
  2. Tisagenlecleucel [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2018.
  3. Grupp SA, Maude SL, Rives S, et al. Updated analysis of the efficacy and safety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia. Blood. 2018;132:895. bloodjournal.org/content/132/Suppl_1/895.
  4. Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449-459. doi: 10.1056/NEJMoa1709919.

3 of 3
Insight from Krishna V. Komanduri, MD—PER Pulse™ Recap:
Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community

Medical Crossfire®: Critical Conversations Between CAR T Centers of Excellence and the Oncology Community is a continuing medical education–certified program. For this program, cochairs Jae H. Park, MD, and Krishna V. Komanduri, MD, were joined by expert faculty Alvaro J. Alencar, MD, and S. Peter Wu, MD, to discuss the implications and clinical applications of noteworthy data, presented at recent international meetings, regarding the treatment of diffuse large B-cell lymphoma (DLBCL), B-cell acute lymphoblastic leukemia (ALL), and other lymphoid malignancies.

This third of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making with regard to appropriate use of chimeric antigen receptor (CAR) T-cell therapy for patients with lymphoid malignancies. Below are some highlights from the activity featuring Dr Komanduri:

  • Tisagenlecleucel is a CD19-directed, genetically modified autologous T-cell immunotherapy indicated for the treatment of patients up to age 25 years with B-cell precursor ALL that is refractory or in second or later relapse and adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy including DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (FL).1
  • Axicabtagene ciloleucel is another CD19-directed, genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from FL.2
  • Potential toxicities with CAR T-cell therapy include cytokine release syndrome, neurotoxicity, and neurologic adverse events (AEs), as well as other AEs including febrile neutropenia, infectious disease, hematologic abnormalities, and cardiopulmonary events.1-3
  • From the initial development of CAR T-cell therapies, there have been important challenges in defining AEs associated with treatment. Over time, and across several treatment centers, the definitions for AE classification have been steadily refined. The most recent criteria are the harmonized American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.3
  • ASTCT consensus guidelines have been developed for the grading of cytokine release syndrome severity, as well as grading the severity of neurologic AEs, in both in adults and children. These grading criteria are important for standardizing the management of CAR T-cell therapy.3

“We developed at harmonized ASTCT consensus grading, and the bottom line is the publication in BBMT [Biology of Blood and Marrow Transplantation] in early 2019. The writing committee consisted of top experts in the field, and they developed a scale for grading of both cytokine release syndrome and neurotoxicity that is very reproducible from individual to individual.”

—Krishna V. Komanduri, MD

References

  1. Tisagenlecleucel [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2018.
  2. Axicabtagene ciloleucel [package insert]. Santa Monica, CA: Kite Pharma, Inc; 2019.
  3. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758.

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