Educational session E06: CAR-T toxicity and management
Tuesday, March 16, 11:00 - 12:15, Auditorium 2
This three-part session on Tuesday will focus on CAR-T toxicity and management.
Dr Patrick Hayden, consultant haematologist and clinical lead for the myeloma service at St James's Hospital, Dublin, Ireland, will discuss EBMT recommendations on this pioneering therapy.
He explains: “Following EMA approval of the first CAR T-cell therapy in 2018, the Practice Harmonization and Guidelines subcommittee of the Chronic Malignancies Working Party proposed the drafting of EBMT best practice recommendations for their use. The EBMT Board accepted the proposal and the authors worked with experts in the field to produce practical clinical recommendations on the management of adults and children receiving autologous CAR T-cell therapy.”
The project involved a series of virtual meetings culminating in a two-day workshop in Lille in 2019. In parallel, a survey was sent to centres active in this field to solicit feedback on current approaches to the topics covered in these guidelines. These recommendations, published in Haematologica in 2020, are intended to reflect current best practice in this novel and rapidly moving field and to support clinicians and other healthcare professionals in delivering consistent, high-quality care.
Dr Hayden says: “The talk focuses on the process followed in the drafting of the guidelines with particular emphasis on the management of early toxicities including CRS and ICANS.”
Also in this session, Dr Miguel Perales (Chief, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA) will discuss neurotoxicity related to CAR T-cell therapy.
He will explain how CD19 target chimeric antigen receptor (CAR) T cells have transformed the treatment landscape of relapsed/refractory (RR) acute lymphoblastic lymphoma, as well as a growing number of non-Hodgkin lymphomas, providing excellent anti-tumour activity and potential cure for these high-risk patients.
However, CAR T-cells are associated with unique immune-mediated toxicities, notably the cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndromes (ICANS). The rate of neurotoxicity recorded in clinical trials of CD19 CAR T-cells ranges from 10% to over 40%. Several factors can impact neurotoxicity including histology, disease burden, cell dose, use of co-stimulatory molecule (CD28 vs. 4-1BB), lymphodepletion regimen, as well as patient factors.
Dr Perales says: “Our understanding of the biology of ICANS is increasing and several biomarkers in the blood and CSF have been identified, including markers of endothelial activation. While the mainstay of current treatment for ICANS remains the use of steroids, guidelines are being developed to better guide use of steroids as well as secondary lines of treatment in patients who don’t respond to steroids.”
In the other presentation in this session, Dr Susana Rives, Paediatric Haematologist at Hospital Sant Joan de Déu de Barcelona, Spain, will discuss cytokine reléase syndrome.
References for Dr Morales talk:
Pennisi M, et al. Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management. Blood Adv. 2020 Feb 25;4(4):676-686.
Wudhikarn K, et al. DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality. Blood Adv. 2020 Jul 14;4(13):3024-3033.
Sheth VS, Gauthier J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant. 2020 Nov 24. Epub ahead of print.
Lee DW, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638.
Santomasso BD, et al. Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2018 Aug;8(8):958-971.
Maus MV, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunother Cancer. 2020 Dec;8(2):e001511.