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The main barrier to CAR T-cell therapy access for your patients with B-cell NHL is:

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Cost of therapy and the complex logistics of treatment access
   
Length of waiting lists/lack of capacity
   
Lack of knowledge about CAR T-cell therapy among HCPs in your region
   
Other
   

Tutorial

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What salvage strategy for CAR T-cell therapy relapse do you use the most in R/R MCL?

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Clinical trials (e.g. with a bispecific antibody)
   
Lenalidomide monotherapy
   
Lenalidomide + rituximab
   
Other
   

Tutorial

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Which of these oncology settings do you predominantly work in?

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Community oncology
   
Academic oncology/oncology research
   
Other
   

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How many patients do you typically refer/treat with CAR T-cell therapy in 1 month?

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0–2
   
3–5
   
>5
   
 
Exploring current treatment strategies for R/R MCL and the role of CAR T-cell therapy
Practicalities of CAR T-cell therapy for MCL in the clinic: Focus on toxicities and salvage therapy
Future considerations for optimizing the use of CAR T-cell therapies in patients with MCL
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Lymphoma, Haematological Malignancies, Haematology CE/CME accredited

touchIN CONVERSATION
A relaxed discussion between two faculty focussed on real world clinical issues. Useful tips below will show how to navigate the activity. Join the conversation. Close

Managing the practicalities of CAR T-cell therapies in patients with R/R MCL: Current considerations and future strategies

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Learning Objectives

After watching this activity, participants should be better able to:

  • Review current treatment strategies for relapsed/refractory mantle cell lymphoma, including the role of CAR T-cell therapy
  • Formulate practical strategies for the management of CAR T-cell-associated toxicities and treatment failure in patients with relapsed/refractory mantle cell lymphoma
  • Discuss future considerations for optimizing CAR T-cell therapy in relapsed/refractory mantle cell lymphoma
Overview

In this activity, haemato-oncologists with expertise in mantle cell lymphoma (MCL) and chimeric antigen receptor (CAR) T-cell therapy respond to questions from the community oncology, haematology and haemato-oncology communities on current treatment strategies for relapsed or refractory MCL and the role of CAR T-cell therapy, managing the toxicities of treatment with CAR T-cells, and future considerations for optimizing the use of CAR T-cell therapies in MCL.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

Haematologists, haemato-oncologists (including CAR T-cell therapy specialists) and oncologists (including community oncologists) involved in the management of mantle cell lymphoma.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Matthew Matasar discloses: Advisory board or panel fees from Genentech and Merck. Consultancy fees from Bayer, Juno Therapeutics, Roche/Genentech, Seattle Genetics, Takeda and Teva. Grants/research support from Bayer, GM Biosciences, Immunovaccine Therapeutics, Janssen, Pharmacyclics, Roche/Genentech and Seagen. Stock/shareholder (self-managed) in Merck. Other financial or material support from ADC Therapeutics, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Epizyme, Immunovaccine Therapeutics, IMV Therapeutics, Janssen, Kite Pharma, Pharmacyclics, Regeneron, Roche, Seagen and Takeda. 

Dr Amitkumar Mehta discloses: Advisory board or panel fees from BeiGene, Gilead, Incyte, MorphoSys and Seagen. Consultancy fees from ADC Therapeutics, Kyowa Kirin, Roche/Genentech and TG Therapeutics. Grants/research support from Bristol Myers Squibb, Forty Seven Inc., Gilead, Incyte, Juno Therapeutics and Takeda. Speaker’s bureau fees from BeiGene, Incyte, Ipsen and Kyowa Kirin and MorphoSys. Other financial or material support from ADC Therapeutics, Affimed, Bristol Myers Squibb, Celgene, Gilead, Innate Pharma, Kite Pharma, Merck, Roche/Genentech, Seagen and TG Therapeutics. 

Content Reviewer

Alicia Canalejo, APRN has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Contributors

Sola Neunie has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 11 January 2024. Date credits expire: 11 January 2025.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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Topics covered in this activity

Lymphoma / Haematological Malignancies / Haematology
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touchIN CONVERSATION
Managing the practicalities of CAR T-cell therapies in patients with R/R MCL: Current considerations and future strategies
1.0 CE/CME credit

Question 1/4
What overall and complete response rates were observed in patients with R/R MCL treated with brexu-cel in the pivotal ZUMA-2 clinical trial?

Brexu-cel, brexucabtagene autoleucel; CR, complete response; ORR, overall response rate; R/R MCL, relapsed or refractory mantle cell lymphoma.

In the ZUMA-2 clinical trial, an ORR of 91% and a CR of 68% was observed for 68 patients with R/R MCL who were treated with brexu-cel, at a median follow-up of 35.6 months.

Abbreviations

Brexu-cel, brexucabtagene autoleucel; CR, complete response; ORR, overall response rate; R/R MCL, relapsed or refractory mantle cell lymphoma.

Reference

Wang M, et al. J Clin Oncol. 2023;41:555–67.

Question 2/4
Your 70-year-old male patient with R/R MCL has relapsed while on second-line acalabrutinib, and is now awaiting CAR T-cell therapy. He has an aggressive disease presentation with a high disease burden and evidence of CNS involvement. What bridging therapy would you choose to help optimize his outcomes with CAR T-cell therapy?

CAR, chimeric antigen receptor; CNS, central nervous system; R/R MCL, relapsed or refractory mantle cell lymphoma.

A 2021 review of bridging therapy options prior to CAR T-cell therapy indicated that rituximab ± cytarabine was suitable for patients with a non-Hodgkin lymphoma and a high disease burden. Blinatumomab and hydroxyurea ± steroids were indicated as suitable bridging therapies for patients with B-cell acute lymphoblastic leukaemia and a high disease burden. Belantamab mafodotin was indicated as a possible bridging therapy for patients with multiple myeloma and a high disease burden.

Abbreviation

CAR, chimeric antigen receptor.

Reference

Bhaskar ST, et al. EJHaem. 2021;3(Suppl. 1):39–45.

Question 3/4
Your patient with R/R MCL has been experiencing recurrent mild infections following treatment with brexu-cel. After routine monitoring, you find that their IgG level is 290 mg/dL. What would you do next?

Brexu-cel, brexucabtagene autoleucel; G-CSF, granulocyte colony-stimulating factor; IgG, immunoglobulin G; IVIG, intravenous immunoglobulin; R/R MCL, relapsed or refractory mantle cell lymphoma.

It is recommended that patients who develop hypogammaglobulinaemia following brexu-cel therapy receive IVIG replacement therapy.1,2 Tocilizumab and corticosteroids are used to manage CRS.1 G-CSF support is used to manage prolonged cytopenias.1 Vaccination with live virus vaccines is not recommended following treatment with brexu-cel, until the immune system has recovered.2

Abbreviations

Brexu-cel, brexucabtagene autoleucel; CRS, cytokine release syndrome; G-CSF, granulocyte colony-stimulating factor; IVIG, intravenous immunoglobulin.

References

1. Thompson JA, et al. J Natl Compr Canc Netw. 2022;20:387–405.

2. FDA. Brexucabtagene autoleucel PI. Available at: www.fda.gov/media/140409/download?attachment (accessed 17 November 2023).

Question 4/4
Off-the-shelf, allogeneic CAR T-cell therapy is currently being investigated to further improve accessibility of the treatment. What is a primary challenge that must be overcome versus autologous CAR T-cell therapy before these therapies can be used in practice?

CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome.

A number of strategies for manufacturing allogeneic CAR T-cell therapies are being investigated. In addition to the risk of GvHD, many production strategies have problems with in vivo T-cell persistence, which negatively impacts efficacy.1 Against these disadvantages, allogeneic CAR-T cell therapy offers the possibilities of large-scale manufacturing and the consequent potential cost reduction, greater standardization of the product, better quality of the therapeutic cells, as well as immediate availability of the product to treat the patients.1 The risk of CRS or ICANS is specific to the patient or their disease characteristics.2

Abbreviations

CAR, chimeric antigen receptor; CRS, cytokine release syndrome; GvHD, graft-versus-host disease; ICANS, immune effector cell-associated neurotoxicity syndrome.

References

1. Aparicio C, et al. Exp Hematol Oncol. 2023;12:73.

2. Thompson JA, et al. J Natl Compr Canc Netw. 2022;20:387–405.

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