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Lymphoma, Multiple Myeloma View Time: 33 mins

touchEXPERT BRIEFING CAR T-cell treatment pathway: From patient identification to long-term management

Watch leading experts discuss CAR T-cell treatment pathways in non-Hodgkin lymphoma and multiple myeloma, from patient identification to long-term management.

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Prof. Ulrich Jäger
Medical University of Vienna, Vienna, Austria

Prof. Ulrich Jäger outlines the potential benefit of CAR T-cell therapy in appropriate patients with non-Hodgkin lymphoma, including how to select suitable patients, making referrals and the benefits of early referral.

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In this interview, we asked Prof. Ulrich Jäger the following questions:

  • In patients with non-Hodgkin lymphoma in clinical trials and in real-world practice, CAR T-cell therapy has resulted in what treatment benefits?
  • What are the most important factors in clinical practice for patient selection for CAR T-cell therapy in non-Hodgkin lymphoma including in transplant ineligible patients?
  • Are there any differences in eligibility criteria for CAR T-cell therapy and autologous stem cell transplant therapy in non-Hodgkin lymphoma?
  • How and when do you refer a patient with non-Hodgkin lymphoma for CAR T-cell therapy?
  • What are the benefits of early referral?
  • Are there any specific regional differences in the selection and management of patients for CAR T-cell therapy?

Ulrich Jäger is a Professor of Hematology at Medizinische Universitsat Wien, Vienna, and Head of the Clinical Department for Hematology and Hemostaseology at the Vienna General Hospital, Vienna, AT. Prof. Jäger obtained his university degree in General Internal Medicine at the University of Vienna. His research interests include lymphoproliferative diseases, chronic lymphocytic leukemia, non-Hodgkin lymphoma, acute lymphocytic leukemia, antibody therapies, and autoimmune hemolytic anemias.

Prof. Ulrich Jäger disclosures: Honoraria/Advisory Boards from Novartis, Janssen, Gilead, BMS/Celgene, Miltenyi, Roche. Grant support from Novartis.

 
Dr Maria-Victoria Mateos
University Hospital of Salamanca, Salamanca, Spain

Dr Maria-Victoria Mateos outlines the potential benefit of CAR T-cell therapy in appropriate patients with multiple myeloma, including data from clinical trials, key factors in selecting patients, and the benefits of early referral.

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In this interview, we asked Dr Maria-Victoria Mateos the following questions:

  • In clinical trials and in real-world practice, patients with multiple myeloma relieving CAR T-cell therapy have demonstrated what treatment benefits?
  • In clinical practice, what are the most important factors for selecting patients with multiple myeloma to receive CAR T-cell therapy?
  • How do the eligibility criteria for CAR T-cell therapy and autologous stem cell transplant therapy differ in patients with multiple myeloma?
  • At what disease stage do you typically see patients treated with CAR T-cell therapy and are there any benefits of patients being referred early?
  • Are there any specific regional differences in the selection and management of patients for CAR T-cell therapy?

Dr María-Victoria Mateos is consultant physician in the Haematology Department and associate professor of Medicine at the University of Salamanca, Spain. She is the director of the Myeloma Program and coordinates the Clinical Trials Unit in Salamanca’s University Hospital Haematology Department. She has published over 250 original papers in international journals.

Dr Maria-Victoria Mateos disclosures: honoraria derived from lectures and participation in boards from Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides, Seagen and BMW/Celgene.

 
Dr Robin Sanderson
King’s College Hospital, London, UK

Dr Robin Sanderson discusses the journey of a patient receiving CAR T-cell therapy including the key steps from collection to infusion, where these stages are managed, and how to manage toxicities.

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In this interview, we asked Dr Robin Sanderson the following questions:

  • Where are the different stages of CAR T-cell therapy both before, during and after an infusion managed including bridging therapy?
  • Please outline the possible short-, medium-and long-term toxicities associated with CAR T-cell therapy?
  • How do you manage the most common CAR T-cell therapy toxicities?
  • What roles do the multidisciplinary team play in assessing patient eligibility, and the identification, management, and long-term monitoring of a patient’s response to CAR T-cell therapy?
  • Are there any specific regional differences in the selection and management of patients for CAR T-cell therapy?

Dr Sanderson is a consultant Haemato-oncologist at King’s College Hospital and has a specialist interest in CAR T-cells, lymphoid disorders, and stem cell transplantation. He completed his medical and haematological training at St Bartholomew’s, King’s College, and Guy’s and St Thomas’ Hospitals, and completed his PhD at Barts Cancer Institute.

Disclosures: Grant funding for advisory board work /travel support from Novartis, Bayer, Roche, Allergan, Moorfields Eye Hospital and has received research funding from Bayer, Novartis, Allergan, BMS and Roche.

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Learning Objectives & Overview
Overview

CAR T-cell therapy has led to improvements in disease outcomes for patients with non-Hodgkin lymphoma and multiple myeloma.1–14
In this activity, leading experts outline the factors and eligibility criteria influencing treatment decisions, the importance of early referral and referral challenges, and the key steps in delivering CAR T-cell therapy, including the management of toxicities.

Learning Objectives

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

  • Outline the potential benefit of CAR T-cell therapy in appropriate patients and how suitable patients can be identified and referred.
  • Describe the patient journey for CAR T-cell therapy.
  • Discuss how patients can be monitored and managed once they have been discharged from hospital.
References
References
  1. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42.
  2. Schuster SJ, Tam CT, Borchmann P, et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(10):1403-1415.
  3. Abramson JS, Palomba ML, Gordon LI, et al, Two-Year Follow-up of Transcend NHL 001, a Multicenter Phase 1 Studyof Lisocabtagene Maraleucel (liso-cel) in Relapsed or Refractory (R/R) Large B-Cell Lymphomas (LBCL). Blood. 2021;138(S1):2840-2840.
  4. Riedell PA, Walling C, Nastoupil LJ, et al. A Multicenter Retrospective Analysis of Clinical Outcomes, Toxicities, and Patterns of Use in Institutions Utilizing Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B-Cell Lymphomas. Blood. 2019;134(S1):1599.
  5. Iacoboni G, Villacampa G, Martinez-Cibrian N, et al. Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Cancer Med. 2021;10(10):3214-3223.
  6. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020;382(14):1331-1342.
  7. Palomba ML, Gordon LI, Siddiqi T, et al. Safety and Preliminary Efficacy in Patients with Relapsed/Refractory Mantle Cell Lymphoma Receiving Lisocabtagene Maraleucel in Transcend NHL 001. Blood. 2020;136 (S1):10–11.
  8. Schuster SJ, Dickinson MJ, Dreyling MH, et al. Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma(r/r FL): Primary analysis of the phase 2Elara trial. J Clin Oncol. 2021 39:15.suppl:7508-750.
  9. Jacobson C, Chavez JC, Sehgal AR, et al. Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel(Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). Blood. 2020;136 (S1):40–41.
  10. Ghione P, Patel A, Bobillo S, et al. A comparison of clinical outcomes from zuma-5 (axicabtagene ciloleucel) and the international scholar-5 external control cohort in relapsed/refractory follicular lymphoma (r/r fl). EHA 2021; June 9, 2021:#LB1904.
  11. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808.
  12. Martin P, Maddocks K, Leonard JP, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;127(12):1559-63.
  13. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716.
  14. Roex G, Timmers M, Wouters K, et al. Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. J Hematol Oncol. 2020;13(1):164.
  15. Moreau P, Kumar SK, San Miguel J, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e105-e118.
  16. Ahmed G, Hamadani M , Shah NN, et al. CAR T-cell therapy for secondary CNS DLBCL. Blood Adv. 2021;5(24):5626-5630.
  17. Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020;4(22):5607-5615.
  18. Rabinovich E, Pradhan K, Sica RA, et al. Elevated LDH greater than 400 U/L portends poorer overall survival in diffuse large B-cell lymphoma patients treated with CD19 CAR-T cell therapy in a real world multi-ethnic cohort. Exp Hematol Oncol. 2021;10(1):55.
  19. Westin JR, Tam CS, Borchmann P, et al. Correlative Analyses of Patient and Clinical Characteristics Associated with Efficacy in Tisagenlecleucel-Treated Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients in the Juliet Trial. Blood. 2019;134(suppl 1):Abstract 4103.
  20. Denlinger N, Bond D, Jaglowski S, et al. CAR T-cell therapy for B-cell lymphoma. Curr Probl Cancer. 2022;46(1):100826.
  21. Hayden PJ, Roddie C, Bader P, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022;33(3):259-275.
  22. Yakoub-Agha I, Chabannon C, Bader P, et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2020;105(2):297-316.
  23. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform Study. Blood. 2021;138 (Supplement 1): 91.
  24. Locke FL, Miklos DB, Jacobson C, et al. Primary Analysis of ZUMA-7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma. Blood. 2021;138 (Supplement 1):2.
  25. Bishop MR, Dickinson M, Purtil D, et al. LBA-6 Tisagenlecleucel Vs Standard of Care As Second-Line Therapy of Primary Refractory or Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma: Analysis of the Phase III Belinda Study. Blood. 2021;138 (Supplement 2):LBA–6.
  26. Gonsalves WI, Buadi FK, Ailawadhi S, et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transplant. 2019;54(3):353–367.
  27. Howell D, Smith A, Appleton S, et al. Multiple myeloma: routes to diagnosis, clinical characteristics and survival - findings from a UK population-based study. Br J Haematol. 2017;177(1):67–71.
  28. Kariyawasan CC, Hughes DA, Jayatillake MM, et al. Multiple myeloma: causes and consequences of delay in diagnosis. QJM. 2007;100(10):635-40.
  29. Snyder S, Chung KC, Jun MP, et al. Access to Chimeric Antigen Receptor T Cell Therapy for Diffuse Large B Cell Lymphoma. Adv Ther. 2021;38(9):4659-4674.
  30. Kansagra A, Farnia S, Majhail N. Expanding Access to Chimeric Antigen Receptor T-Cell Therapies: Challenges and Opportunities. Am Soc Clin Oncol Educ Book. 2020;40:1-8.
  31. Gajra A, Jeune-Smith Y, Feinberg BA. Barriers to Referral for Chimeric Antigen Receptor T Cell (CAR-T) Therapies Among U.S. Community Hematologists/Oncologists (cH/O). Blood. 2021;138(S1):4010.
  32. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47-62.
  33. Mahmoudjafari Z, Hawks KG, Hsieh AA, et al. American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group Survey on Chimeric Antigen Receptor T Cell Therapy Administrative, Logistic, and Toxicity Management Practices in the United States. Biol Blood Marrow Transplant. 2019;25(1):26-33.
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