Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events.

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as 'living drugs,' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.
Competing Interests: Competing interests: CC─Consultant and/or advisory board: Novartis. MLD─Consultant and/or advisory board: Celyad, Novartis; Research/license support: Atara, Celgene; Stock option: Adaptive Biotechnologies, Precision Bioscience. CD─ Consultant and/or advisory board: Evidera, Juno. JD─Consultant and/or advisory board: Unum Therapeutics, Blue Earth Diagnostics; Royalties: Wolters Kluwer. JCF─NIDDK 23 grant. MJF─Consultant and/or advisory board: Arcelex, Celgene, Nkarta, Novartis, Xenetic Bio. JLH-C─At-large board member: ASTCT; Vice Chair: Government affairs, Task force member on Immunotherapies and Palliative Care, ASH; Co-Primary Investigator: Imaging trial haplo/cord, graft failure NHLBI RO1 grant. SAG─Consultant and/or advisory board: Adaptimmune, Allogene, Cellectis, Eureka, GlaxoSmithKline, Humanigen, J&J/Janssen, Juno, Novartis, Roche, TCR2, Vertex/CRISPR Therapeutics; Grant/research support: Kite Gilead, Novartis, Servier, Vertex. KVK─Consultant or SAB: Kite/Gilead, Autolus, Juno/BMS, Celgene, Novartis, Takeda, Kiadis, Incyte, Atara, Legend, Kadmon, Helocyte; Clinical trials support (institutional): Kite/Gilead, Novartis, Atara, Allogene; Nonprofit organizations: National Marrow Donor Program (Board of Directors), ASTCT (Chair, cell therapy committee). DWL─Owner: Immchase, LLC; Consultant and/or advisory board: ACI Clinical (on behalf of Celgene), Harpoon Therapeutics, Juno Therapeutics. FLL─Scientific advisor: Kite/Gilead, Novartis, BMS/Celgene, Allogene, Wugen, Calibr, Gamma Delta Therapeutics; Consultant: Cellular Biomedicine Group Inc; Research support: Kite/Gilead. SLM─Consultant and/or advisory board: Kite, Novartis. MVM─Consultant and/or advisory board: Adaptimmune, Adaptive Biotechnologies, Argentus, BD Sciences, Bluebird Bio, Cell Signaling, Collectis (SAB), CRISPR Therapeutics, EMD Serono, Inysus, Kite, Juno, MPM, Novartis, Takeda, TCR2 (SAB), Third Rock Ventures, WindMIL (SAB); Grant/research support: CRISPR Therapeutics, Kite Gilead. PLM─Consultant and/or advisory board: BlueBird Biotech, BMS, Celgene, Fate Therapeutics, Janssen, Juno, Karyopharm, Magenta Therapeutics, MedScape, Sanofi, Takeda. SSN─Consultant and/or advisory board: Celgene, Cell Medica, Incyte, Kite/Gilead, Merck, Novartis, Pfizer, Precision Biosciences, Unum Therapeutics; Grant/research support: Acerta, BMS, Collectis, Karus, Kite Gilead, Merck, Poseida, Unum Therapeutics. TGN─Consultant on imaging: Parexel, Intrinsic Imaging; SAB on Checkpoint and Myocarditis: BMS; Consultant: H3 Biomedicine, Aprea Therapeutics. BDS─Consultant and/or advisory board: Kite Gilead, Juno/Celgene, Insysus, Novartis, Janssen; Grant/research support: ADC Therapeutics. EJS─Consultant and/or advisory board: Adaptimmune, Cellgene, Magenta, Novartis, Partner Therapeutics. DTT─Advisory board: La Roche, Amgen, Janssen, Novartis. CJT─Consultant and/or advisory board: Aptevo, Arsenal Bio, AstraZeneca, Caribou Biosciences, Century Therapeutics, Eureka Therapeutics, Humanigen, Juno/BMS, Kite/Gilead, Myeloid Therapeutics, Nektar Therapeutics, Novartis, Precision Biosciences, T-CURX; Stock options: Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Arsenal Bio, Myeloid Therapeutics; Grant/research support: Juno/BMS, Nektar Therapeutics, AstraZeneca. SA, MRB, JNB, TJF, EM, and TW─Nothing to disclose. SITC staff: AK, BL, LL and SMW─Nothing to disclose.
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