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Unanswered questions following reports of secondary malignancies after CAR-T cell therapy

Nature Medicine volume 30, pages 338–341 (2024)Cite this article

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Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

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References

  1. Harrison, S. J. Blood 142 (suppl. 1), 6939 (2023).

    Article  Google Scholar 

  2. Li, P. et al. Blood 142 (suppl. 1), 1025 (2023).

    Article  Google Scholar 

  3. Heinrich, T. et al. Mol. Ther. 21, 1160–1168 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Micklethwaite, K. P. et al. Blood 138, 1391–1405 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hsieh, E. M. et al. Blood Adv. 6, 5222–5226 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Anand, K. et al. J. Immunother. Cancer 8, e000104 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chihara, D., Dores, G. M., Flowers, C. R. & Morton, L. M. Blood 138, 785–789 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Meadows, A. T. et al. J. Clin. Oncol. 27, 2356–2362 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brown, J. R. et al. J. Clin. Oncol. 23, 2208–2214 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Schaapveld, M. et al. N. Engl. J. Med. 373, 2499–2511 (2015).

    Article  CAS  PubMed  Google Scholar 

  11. Spencer Chapman, M. et al. Nat. Med. 29, 3175–3183 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lamble, A. J. et al. Blood Adv. 7, 575–585 (2023).

    Article  CAS  PubMed  Google Scholar 

  13. Hamilton, M. P. et al. Am. Soc. Hematol. https://go.nature.com/3GKUITY (2023).

  14. Steffin, D. H. M. et al. Blood 140, 16–24 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cornetta, K. et al. Mol. Ther. 31, 801–809 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the executive committees of the ASTCT, EBMT and ISCT for reviewing this commentary. B.L.L. is an immediate past president of the ISCT. D.L.P. is vice president of the ASTCT. M.P.G. is co-chair of the Immuno & Gene Therapy Committee of the ISCT. J.J.B. is co-chair of the Stem Cell Engineering Committee of the ISCT. M.V.M. is chair and F.L.L. is co-chair of the ASTCT Committee on Cellular Therapy. A.M.S. is president of the EBMT. M.-A.P. is president of the ASTCT.

Author information

Authors and Affiliations

  1. Center for Cellular Immunotherapies and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA

    Bruce L. Levine & Carl H. June

  2. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Marcelo C. Pasquini

  3. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    Marcelo C. Pasquini

  4. Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA

    John E. Connolly

  5. Cell Therapy and Transplant, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    David L. Porter

  6. Department of Laboratory Medicine and Pathology, Mayo Clinic in Arizona, Phoenix, AZ, USA

    Michael P. Gustafson

  7. Transplantation and Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jaap J. Boelens

  8. Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    Edwin M. Horwitz

  9. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Stephan A. Grupp

  10. Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Stephan A. Grupp

  11. Cellular Immunotherapy Program, Mass General Cancer Center and Harvard Medical School, Cambridge, MA, USA

    Marcela V. Maus

  12. Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA

    Frederick L. Locke

  13. University Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute Milano, Milan, Italy

    Fabio Ciceri

  14. Hematology and BMT unit, IRCCS San Raffaele scientific institute, Milano, Italy

    Annalisa Ruggeri

  15. Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    John Snowden

  16. Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK

    John Snowden

  17. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    Helen E. Heslop

  18. Texas Children’s Hospital and Houston Methodist Hospital, Houston, TX, USA

    Helen E. Heslop

  19. Center for Cancer Cell Therapy, Stanford Cancer Institute and Departments of Pediatrics and Medicine, Stanford University, Palo Alto, CA, USA

    Crystal L. Mackall

  20. Parker Institute for Cancer Immunotherapy, Palo Alto, CA, USA

    Crystal L. Mackall

  21. Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June

  22. Clinical Hematology Department, Institut Català d’Oncologia – L’Hospitalet, IDIBELL, University of Barcelona, Barcelona, Spain

    Anna M. Sureda

  23. Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Miguel-Angel Perales

  24. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Miguel-Angel Perales

Authors
  1. Bruce L. Levine
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  2. Marcelo C. Pasquini
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  3. John E. Connolly
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  4. David L. Porter
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  5. Michael P. Gustafson
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  6. Jaap J. Boelens
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  7. Edwin M. Horwitz
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  8. Stephan A. Grupp
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  9. Marcela V. Maus
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  10. Frederick L. Locke
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  11. Fabio Ciceri
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  12. Annalisa Ruggeri
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  13. John Snowden
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  14. Helen E. Heslop
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  15. Crystal L. Mackall
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  16. Carl H. June
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  17. Anna M. Sureda
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  18. Miguel-Angel Perales
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Corresponding author

Correspondence to Bruce L. Levine.

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Competing interests

B.L.L. is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives license revenue from such licenses; is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics; and a member of the scientific advisory boards of Akron Biotech, Avectas, Capstan Therapeutics, Cellula Therapeutics, Immuneel Therapeutics, Immusoft, In8bio, Kite Gilead, Ori Biotech, Oxford Biomedica, ThermoFisher Pharma Services, UTC Therapeutics and Vycellix. M.C.P. received research support from Novartis, Kite Pharma, Bristol Myers Squibb, Janssen Consulting: Novartis and Gilead. J.E.C. is a cofounder of Twain Therapeutics, director at Dispatch Therapeutics and 3T Biosciences, and receives research funding from Janssen. D.L.P. reports stock and other ownership interests from Genentech, Roche (spouse former employment); consulting or advisory roles from Novartis, Kite/Gilead, Gerson Lehrman Group and Janssen (Johnson & Johnson), Bristol-Myers Squibb, Bluebird Bio, Angiocrine, Mirror Biologics, Capstan Therapeutics, Instill Bio, Sana Biotechnology and Verismo Therapeutics; received research funding from Novartis and Bristol-Myers Squibb; and reports royalties and other intellectual property from Novartis and Tmunity. D.L.P. is a patent inventor for use of CAR-T cells in CD19+ malignancies, and was chair of the board of directors of the National Marrow Donor Program from October 2018 to October 2020. J.J.B. reports consulting fees from Sanofi, Sobi, SmartImmune, Immusoft, BlueRock, Advanced Clinical, Merck and Bluebird Bio. S.A.G. declares research and/or clinical trial support from Novartis, Servier, Vertex, Cellectis and Kite; and was a member of steering committees, scientific advisory boards or held consulting positions at Novartis, Allogene, Adaptimmune, GlaxoSmithKline, Vertex, Jazz, Kyttaro and Cabaletta. M.V.M. is an inventor on patents related to adoptive cell therapies, held by Massachusetts General Hospital (some licensed to Promab) and the University of Pennsylvania (some licensed to Novartis); reports grant or research support from Kite Pharma and Moderna; reports consulting fees from several companies involved in cell therapies; has equity in 2SeventyBio, A2Bio, Cargo, Century Therapeutics, Neximmune, Oncternal and TCR2; and has served on the board of directors for 2Seventy Bio. F.L.L. has had consulting or advisory roles for Allogene, Amgen, Bluebird Bio, BMS/Celgene, Calibr, Cellular Biomedicine Group, Cowen, ecoR1, Emerging Therapy Solutions Gerson Lehman Group, GammaDelta Therapeutics, Iovance, Janssen, Kite, a Gilead Company, Legend Biotech, Novartis, Umoja and Wugen; serves on a data safety monitoring board for the NCI; receives research funding from Allogene, Kite, BMS, 2seventyBio and Novartis; and has patents and other intellectual property in the field of cellular immunotherapy held by Moffitt Cancer Center. H.E.H. has equity in Marker Therapeutics, Allovir, and CoRegen and serves on scientific advisory boards for March Biosciences, Fresh Wind Biotechnologies and Tikva Allocell. C.L.M. is an inventor on multiple patents related to CAR-T cell therapy and has received royalties for licenses to Juno Therapeutics and CARGO therapeutics. C.L.M. is a co-founder of Lyell Immunopharma, CARGO Therapeutics and Link Cell Therapies, which are developing CAR-T cells and holds equity in these companies. C.L.M. is a consultant for CARGO, Link, Immatics, Ensoma, Adaptimmune and received research funding from Lyell and Tune Therapeutics. C.H.J. is an inventor on patents and/or patent applications licensed to Novartis and receives license revenue from such licenses. C.H.J. is a scientific founder of Tmunity Therapeutics, Dispatch Biotherapeutics, Bluewhale Bio, Marble Therapeutics and Capstan Therapeutics; is a member of the scientific advisory boards of AC Immune, BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Cellcarta, Celldex, Danaher, Decheng, ImmuneSensor, Kite Gilead, Poseida, Replay Bio, Treadwell Therapeutics, Verismo, Viracta, Vittoria and WIRB-Copernicus; and receives sponsored research support from Kite Gilead. A.M.S. has received research support from Takeda, and honoraria from Takeda, BMS/Celgene, MSD, Novartis, Gilead Kite, Sanofi, Pierre Fabre, Janssen and Jazz Pharmaceuticals. M.-A.P. reports honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Sanofi, Syncopation, VectivBio AG and Vor Biopharma; serves on data safety and monitoring boards for Cidara Therapeutics, Medigene and Sellas Life Sciences; and the scientific advisory board of NexImmune. M.-A.P. has ownership interests in NexImmune, Omeros and OrcaBio, and has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics and Novartis. M.C.G., E.M.H., F.C., A.R. and J.S. all have nothing to disclose.

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Levine, B.L., Pasquini, M.C., Connolly, J.E. et al. Unanswered questions following reports of secondary malignancies after CAR-T cell therapy. Nat Med 30, 338–341 (2024). https://doi.org/10.1038/s41591-023-02767-w

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