EC Clinical and Medical Case Reports

Research Article Volume 6 Issue 5 - 2023

Systematic Review Reflecting the Magic Role of CART - cell in Central Nervous System with Secondary Lymphomas

Ghada ELGohary1*, Karim Mohamed ELshatoury2 and Riad El Fakih3

1Professor Adult Hematology/Stem Cell Transplant, Internal Medicine Department, Faculty of Medicine, Ain Shams University Hospitals, Cairo, Egypt

2Faculty of Health Sciences with Honour Specialization in Kinesiology, University of Western, Ontario, Canada

3King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

*Corresponding Author: Ghada ELGohary, Professor Adult Hematology/Stem Cell Transplant, Internal Medicine Department, Faculty of Medicine, Ain Shams University Hospitals, Cairo, Egypt.
Received: March 23, 2023; Published: May 01, 2023



Background: Chimeric antigen receptor T (CAR-T) cell therapy is an approved, safe and effective therapy for patients with non-Hodgkin’s lymphoma.

Aim: The current study sought to determine if secondary CNS lymphoma patients will safely benefit from CAR T-cell therapy.

Materials and Methods: Two independent raters separately examined PubMed, Web of Science, Embase, and the Cochrane library for all records relating to CAR T-cell therapies (i.e. Axi-cel and Tisa-cel) published prior to May 19, 2022. Included were studies that investigated secondary CNS lymphoma patients treated with CAR T-cell and reported the (Their) effectiveness and safety. Six cohort observational studies were included. A method “(RoB 2.0) tool for observational studies” developed expressly to assess the risk of bias was employed.

Results: Studies were symmetrically distributed, no publication bias. < 20% missing data. (According to current data) CAR-T cell therapy resulted in long-term remission in individuals with secondary CNS lymphoma, according to current data. The results for 872 patients in six trials showed 45 patients with CNS involvement, 827 with no CNS involvement, an ORR in 619 patients (16 of them with CNS involvement) and CR rate in 490 patients (18 with CNS involvement) mean estimate of 73.5% (95% CI, 36.5 ‑ 82%) and 62.5% (95% CI, 39.5 ‑ 64%), respectively. In patients with CNS involvement the CRS “Grade ≥ 3” was 6/45 (30.9%, 21 - 68%) and the ICANS rate was 8/45 (17.7%, 9.8 - 30.2%). The ICU admission was 12/45 (30.31%, 29 - 51%). The progression of the disease/death was reported for 136 patients with BCL from the six selected studies, and reported in one case with CNS involvement. The “progression of the disease/death” pooled “OR” (95% CI) was 14.35% (8.5 - 36.2%).

Conclusion: Patients with secondary CNS lymphoma may benefit from CAR-T cell therapy, with manageable toxicities. As a result, CAR-T cell therapy has the potential to be a therapeutic option for lymphoma patients with CNS involvement. Prospective research with bigger samples and longer follow-up periods are needed.

Keywords: Efficacy; Safety; CAR; T-Cell; Therapies; Lymphoma; Central Nervous System

  1. Padala SA and Kallam A. “Diffuse Large B Cell Lymphoma”. In: Stat Pearls. Treasure Island (FL): Stat Pearls Publishing (2022).
  2. Galli J and Greenlee J. “Paraneoplastic Diseases of the Central Nervous System”. F1000Research (2020): 9.
  3. Zhang J., et al. “Impact of rituximab on incidence of and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: a systematic review and meta-analysis”. Leukemia and Lymphoma 3 (2014): 509-514.
  4. Tai WM., et al. “Central nervous system (CNS) relapse in diffuse large B cell lymphoma (DLBCL): pre-and post-rituximab”. Annals of Hematology 90 (2011): 809-818.
  5. Karschnia P., et al. “Primary Dural Lymphomas: Clinical Presentation, Management, and Outcome”. Cancer 126 (2020): 2811-2820.
  6. El-Galaly TC., et al. “Treatment Strategies, Outcomes and Prognostic Factors in 291 Patients with Secondary CNS Involvement by Diffuse Large B-Cell Lymphoma”. The European Journal of Cancer 93 (2018): 57-68.
  7. Ostrom QT., et al. “CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011-2015”. Neuro-Oncology 20 (2018): iv1-iv86.
  8. Han CH and Batchelor TT. “Diagnosis and Management of Primary Central Nervous System Lymphoma”. Cancer 123 (2017): 4314-4324.
  9. Sehn LH., et al. “Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B‑cell lymphoma in British Columbia”. Journal of Clinical Oncology 223 (2005): 5027‑
  10. Coiffier B. “Rituximab in the treatment of diffuse large B‑cell lymphomas”. Seminars in Oncology 29 (2002): 30‑
  11. Habermann TM., et al. “Rituximab‑CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B‑cell lymphoma”. Journal of Clinical Oncology 24 (2006): 3121‑
  12. Sarkozy C and Sehn LH. “Management of relapsed/refractory DLBCL”. Best Practice and Research Clinical Haematology 31 (2018): 209‑
  13. Damaj G., et al. “Late relapse of localized high‑grade non‑hodgkin's lymphoma: Clinical and biological features”. Blood 112 (2008): 2603-2603.
  14. Larouche JF., et al. “Lymphoma recurrence 5 years or later following diffuse large B‑cell lymphoma: Clinical characteristics and outcome”. Journal of Clinical Oncology 28 (2010): 2094‑
  15. Kumar A., et al. “Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: findings from a large national database”. Cancer 11 (2012): 2944-2951.
  16. Glass J., et al. “Preirradiation Methotrexate Chemotherapy of Primary Central Nervous System Lymphoma: Long-Term Outcome”. Journal of Neurosurgery 81 (1994): 188-195.
  17. Houillier C., et al. “Management and Outcome of Primary CNS Lymphoma in the Modern Era: An LOC Network Study”. Neurology 94 (2020): e1027-e1039.
  18. Karschnia P., et al. “Pharmacologic Management of Cognitive Impairment Induced by Cancer Therapy”. The Lancet Oncology 20 (2019): e92-e102.
  19. Neelapu SS., et al. “Chimeric antigen receptor T-cell therapy - assessment and management of toxicities”. Nature Reviews Clinical Oncology 1 (2018): 47-62.
  20. Savoldo B., et al. “CD28 Costimulation Improves Expansion and Persistence of Chimeric Antigen Receptor–Modified T Cells in Lymphoma Patients”. Journal of Clinical Investigation 121 (2011): 1822-1826.
  21. Schuster SJ., et al. “Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma”. The New England Journal of Medicine 380 (2019): 45-56.
  22. Maude SL., et al. “Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia”. The New England Journal of Medicine 378 (2018): 4394-4348.
  23. Wang M., et al. “KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma”. The New England Journal of Medicine 382 (2020): 1331-1342.
  24. Deckert M., et al. “Systems Biology of Primary CNS Lymphoma: From Genetic Aberrations to Modeling in Mice”. Acta Neuropathologica 127 (2014): 175-188.
  25. Giannini C., et al. “CNS Lymphoma: A Practical Diagnostic Approach”. Journal of Neuropathology and Experimental Neurology 73 (2014): 478-494.
  26. Lee DW., et al. “Current concepts in the diagnosis and management of cytokine release syndrome”. Blood 124 (2014): 188‑
  27. Page MJ., et al. “The PRISMA 2020 statement: an updated guideline for reporting systematic reviews”. Systematic Reviews 1 (2021): 89.
  28. Sterne JAC., et al. “RoB 2: a revised tool for assessing risk of bias in randomised trials”. British Medical Journal 366 (2019): l4898.
  29. Ma LL., et al. “Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?” Military Medical Research (2020).
  30. Juni P., et al. “Systematic reviews in health care: assessing the quality of controlled clinical trials”. British Medical Journal 7303 (2001): 42-46.
  31. Moher D., et al. “Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement”. PLOS Medicine 7 (2009): e1000097.
  32. Frigault MJ., et al. “Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial”. Blood 15 (2022): 2306-2315.
  33. Wudhikarn K., et al. “DLBCL Patients Treated with CD19 CAR T Cells Experience a High Burden of Organ Toxicities but Low Nonrelapse Mortality”. Blood Advances 4 (2020): 3024-3033.
  34. Kochenderfer JN and Rosenberg SA. “Treating B‑cell cancer with T cells expressing anti‑CD19 chimeric antigen receptors”. Nature Reviews Clinical Oncology 10 (2013): 267‑
  35. Jensen MC., et al. “Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19‑specific chimeric antigen receptor redirected T cells in humans”. Biology of Blood and Marrow Transplantation 16 (2010): 1245‑
  36. Savoldo B., et al. “CD28 costimulation improves expansion and persistence of chimeric antigen receptor‑modified T cells in lymphoma patients”. Journal of Clinical Investigation 121 (2011): 1822‑
  37. Till BG., et al. “Adoptive immunotherapy for indolent non‑hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20‑specific T cells”. Blood 112 (2008): 2261‑
  38. Neelapu SS., et al. “Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma”. The New England Journal of Medicine 26 (2017): 2531-2544.
  39. Schuster SJ., et al. “Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma”. The New England Journal of Medicine 1 (2019): 45-56.
  40. Jacoby E., et al. “CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study”. Leukemia6 (2022): 1525-1532.
  41. Abbasi A., et al. “Axicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis”. Journal of Hematology and Oncology 1 (2020).
  42. Frigault MJ., et al. “Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma”. Blood 11 (2019): 860-866.
  43. Novo M., et al. “Axicabtagene Ciloleucel Chimeric Antigen Receptor T Cell Therapy in Lymphoma with Secondary Central Nervous System Involvement”. Mayo Clinic Proceedings 11 (2019): 2361-2364.
  44. Frigault MJ., et al. “Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma”. Blood11 (2019): 860-866.
  45. Ahmed G., et al. “CAR T-cell therapy for secondary CNS DLBCL”. Blood Advances 24 (2021): 5626-5630.
  46. Abramson JS., et al. “Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study”. Lancet10254 (2020): 839-852.
  47. Ghafouri S., et al. “Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience”. Clinical Lymphoma, Myeloma and Leukemia 12 (2021): 861-872.
  48. Holtzman NG., et al. “Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes”. Neuro-Oncology 1 (2021): 112-121.
  49. Jacobson CA., et al. “Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity”. Journal of Clinical Oncology 27 (2020): 3095-3106.
  50. Nastoupil LJ., et al. “Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results from the US Lymphoma CAR T Consortium”. Journal of Clinical Oncology 27 (2020): 3119-3128.
  51. Strati P., et al. “Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma”. Blood Advances 16 (2020): 3943-3951.

Ghada ELGohary., et al. "Systematic Review Reflecting the Magic Role of CART - cell in Central Nervous System with Secondary Lymphomas." EC Clinical and Medical Case Reports   6.5 (2023): 188-206.