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. 2025 Dec 9;9(23):6047-6058.
doi: 10.1182/bloodadvances.2025017011.

International consensus guidelines for the conduct and reporting of CAR T-cell clinical trials in AML

Swati Naik  1 , Richard Aplenc  2 , Susanne H C Baumeister  3   4   5 , Marco Becilli  6 , Anand S Bhagwat  2   7 , Challice L Bonifant  8 , Lihua E Budde  9 , Christopher D Chien  10 , Kevin J Curran  11 , Anthony F Daniyan  12 , Alexandra Dreyzin  10   13 , Rebecca A Gardner  14 , Sara Ghorashian  15 , Stephen Gottschalk  1 , LaQuisa C Hill  16   17   18 , M Eric Kohler  19 , Adam Lamble  20 , Franco Locatelli  6   21 , Maksim Mamonkin  16   18 , Bilal Omer  16   18 , Jae H Park  22 , Concetta Quintarelli  6   23 , Benedetta Rambaldi  24 , Rebecca M Richards  25 , David A Sallman  26 , Tim Sauer  27 , Nirali N Shah  10 , Marion Subklewe  28   29 , Corinne Summers  20 , Sarah K Tasian  2   30   31 , Naomi Taylor  10 , Sarah Tettamanti  32 , Michael R Verneris  19 , M Paulina Velasquez  1 , Saar I Gill  33
Affiliations

International consensus guidelines for the conduct and reporting of CAR T-cell clinical trials in AML

Swati Naik et al. Blood Adv. .

Abstract

Early clinical experience with the use of chimeric antigen receptor (CAR) T-cell therapies for patients with acute myeloid leukemia (AML) has been beset by high rates of toxicities and low rates of response. We convened an international workshop with the goal of bringing investigators in the field of AML-directed CAR T-cell therapy together to facilitate discussion of challenges and to brainstorm potential solutions. Based on discussions at the workshop, it was evident that (1) treating and targeting AML with CAR T cells is associated with unique clinical challenges, and (2) variability in clinical trial design, definitions of toxicities, correlative data collection, and reporting methods hinders the field's ability to compare study outcomes and to develop best practices. Further, details of fundamental CAR T-cell attributes and key correlates of efficacy and toxicity were not uniformly reported in published studies, limiting understanding of barriers to success. These observations led to a concerted team effort in which experts in basic/translational science and clinical investigation from pediatric and adult centers worked together to streamline key attributes of clinical trial design and reporting. Consensus criteria were discussed and agreed upon, leading to the creation of a white paper. These guidelines aim to bolster the overall quality of AML-directed CAR T-cell research, allow for comparisons across trials, and inform the next phase of development of AML-directed CAR T-cell therapies that we hope will improve patient outcomes.

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Conflict of interest statement

Conflict-of-interest disclosure: S.H.C.B. reports that their spouse is a former employee of Takeda Pharmaceuticals and Alexion Pharmaceuticals; and has received salary and stock/stock options unrelated to this work. C.L.B. reports holding pending patents in the field of engineered cell therapies. L.E.B. serves as a consultant for Genentech, MustangBio, Roche, AstraZeneca, Amgen, Merck, and ADC Therapeutics. K.J.C. reports consultancy for Novartis; board membership and equity in Turn Bio and PromiCell; and research funding from Novartis, Cellectis, and Atara Biotherapeutics. A.F.D. reports enlistment as an inventor on multiple patents related to chimeric antigen receptor (CAR) T-cell therapy; possible eligibility to receive a portion of royalties paid to Memorial Sloan Kettering (MSK) by Caribou Biosciences Inc, Tigen Pharma SA, and PromiCell Therapeutics Inc; financial interests as the chief scientific officer of PromiCell Therapeutics Inc; and advisory consultancy for Shoreline Biosciences Inc. R.A.G. reports patents related to CAR T-cell technologies licensed to Bristol Myers Squibb (BMS). S. Ghorashian reports affiliations with Autolus Ltd and related patents; membership on the data safety monitoring board of Immatics; scientific advisory board membership for Be Biopharma; consultancy for Cargo Therapeutics within the last 12 months; and patents and patent applications in the fields of T-cell and/or gene therapy for cancer. L.C.H. reports being on the advisory board of March Biosciences; membership in the speakers bureau of Kite/Gilead; and honoraria from Sanofi. F.L. reports honoraria from and/or membership in the speakers bureau for Novartis, Jazz Pharmaceuticals, Sanofi, Sobi, Miltenyi Biotec, bluebird bio, Inc, Amgen, and BMS; and has participated in an advisory board for Amgen and Vertex. M.M. reports being a cofounder with equity and a director at March Biosciences; patent fees from Fate Therapeutics, Beam Therapeutics, and March Biosciences; research support from Fate Therapeutics and March Biosciences; and advisory board membership for NKILT Therapeutics and March Biosciences. B.O. reports patents in cell therapy unrelated to this study. J.H.P received consulting fees from Adaptive Biotechnologies, AffyImmune Therapeutics, Allogene Therapeutics, Amgen, Artiva Biotherapeutics, Ascentage Pharma, Autolus, BeiGene, Bright Pharmaceutical Services, Inc, Caribou Biosciences, Curocell, Kite Pharma, Galapagos, Iovance Biotherapeutics, Jazz Pharmaceuticals, Medpace, Pfizer, Servier, Sobi, Synthekine, and Takeda. C.Q. reports patent applications in the field of CAR T cells. D.A.S. reports consultancy for AbbVie, Agios, Debiopharm, Janssen Pharmaceuticals, Johnson & Johnson, Molecular Partners, and Novartis; advisory board membership for AbbVie, Agios, AvenCell, Astellas Pharma, bluebird bio, BMS, Dark Blue Therapeutics, Geron, Novartis, Shattuck Labs, Servier, Syndax, Syros, and Taiho Oncology; and research funding from Aprea Therapeutics and Jazz Pharmaceuticals. N.N.S. reports research funding from Lentigen, Vor Bio, and Cargo Therapeutics; attending advisory board meetings (no honoraria) for Vor Bio, ImmunoACT, and Sobi; royalties from Cargo Therapeutics; and was supported in part by the Intramural Research Program, Center for Cancer Research, National Cancer Institute and National Institutes of Health Clinical Center, National Institutes of Health (ZIA BC 011927). M.S. receives industry research support from Amgen, BMS/Celgene, Gilead/Kite, Johnson & Johnson, Miltenyi Biotec, Novartis, Roche, Seattle Genetics, and Takeda; serves as a consultant/advisor to AbbVie, Crossbow Therapeutics, Debiopharm, Gilead/Kite, Interius, Johnson & Johnson, Molecular Partners, Novartis, and Otsuka; and serves on the speakers bureau at Amgen, BMS/Celgene, Gilead/Kite, Miltenyi Biotec, Novartis, Roche, and Takeda. S.K.T. reports research funding from Beam Therapeutics, Incyte Corporation, and Kura Oncology; serves or has served on scientific advisory boards for Aleta Biotherapeutics, AstraZeneca, Jazz Pharmaceuticals, Kestrel Therapeutics, Kura Oncology, Novartis, Syndax Pharmaceuticals, and Wugen, Inc; and has received travel support from Amgen and Jazz Pharmaceuticals. S.K.T was supported by the Andrew McDonough B+ Foundation for Childhood Cancer Research; is a Scholar of the Leukemia & Lymphoma Society; and holds the Joshua Kahan Endowed Chair in Pediatric Leukemia Research at the Children’s Hospital of Philadelphia. M.P.V. has patent applications in the field of T-cell and/or gene therapy for cancer; and is a member of the Rally! Foundation medical advisory board. S.I.G. reports being a named inventor on intellectual property related to CAR T cells in AML, including patents licensed to Novartis; is a scientific cofounder and holds equity in Interius Biotherapeutics and Carisma Therapeutics; and reports being a scientific advisor to Carisma Therapeutics, Cartography Biosciences, Currus, Interius, Kite, NKILT Therapeutics, and Mission Bio. The remaining authors declare no competing financial interests.

Figures

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Graphical abstract
Figure 1.
Figure 1.
Outline of key recommendations for conduct and reporting of AML CAR clinical trials.
See this image and copyright information in PMC

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