{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:34:24Z","timestamp":1793284464650,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of hematologic malignancy-associated somatic mutations in patients without hematologic malignancies. In multiple myeloma (MM), the implications of CHIP on chimeric antigen receptor (CAR)-T cell outcomes and toxicities have yet to be fully explored. In a retrospective study at UCLA, we explored the association between CHIP and clinical outcomes of 68 adult patients with MM (31% with CHIP mutations) who were undergoing CAR-T cell therapy from 6\/1\/2021 to 12\/31\/2024. The overall (95% CHIP vs. 93% no CHIP;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.99) and complete response rates (81% CHIP vs. 67% no CHIP;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.15) did not differ by CHIP status. Similarly, CHIP mutations did not impact progression-free survival (HR 0.83; 95% CI 0.38\u20131.83;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.65) or overall survival (HR 0.76; 95% CI 0.24\u20132.45;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.65). Patients with CHIP mutations were more likely to develop CRS (100% vs. 70%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007); however, there was no difference in the incidence of ICANS (33% CHIP vs. 17% no CHIP,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.20). Our results show that although CHIP did not negatively influence response rate, complete response rate, survival, or progression-free survival in MM patients after CAR-T cell therapy, it did confer a higher risk of inflammatory response with increased frequency and grade of CRS.\n                  <\/jats:p>","DOI":"10.1007\/s12185-026-04249-4","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T05:49:04Z","timestamp":1784353744000},"page":"670-679","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of clonal hematopoiesis of indeterminate potential on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy"],"prefix":"10.1007","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6686-1494","authenticated-orcid":false,"given":"Sophie G.","family":"Carlson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Puliafito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Niroshi","family":"Senaratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasha","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Timmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"4249_CR1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a006251","author":"EA Goldman","year":"2023","unstructured":"Goldman EA, Spellman PT, Agarwal A. Defining clonal hematopoiesis of indeterminate potential: evolutionary dynamics and detection under aging and inflammation. Mol Case Stud. 2023. https:\/\/doi.org\/10.1101\/mcs.a006251.","journal-title":"Mol Case Stud"},{"issue":"1","key":"4249_CR2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1182\/blood-2015-03-631747","volume":"126","author":"DP Steensma","year":"2015","unstructured":"Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9\u201316.","journal-title":"Blood"},{"key":"4249_CR3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.yjmcc.2021.07.004","volume":"161","author":"CS Marnell","year":"2021","unstructured":"Marnell CS, Bick A, Natarajan P. Clonal hematopoiesis of indeterminate potential (CHIP): linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease. J Mol Cell Cardiol. 2021;161:98\u2013105.","journal-title":"J Mol Cell Cardiol"},{"key":"4249_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.104187","volume":"192","author":"DI Nathan","year":"2023","unstructured":"Nathan DI, Dougherty M, Bhatta M, Mascarenhas J, Marcellino BK. Clonal hematopoiesis and inflammation: a review of mechanisms and clinical implications. Crit Rev Oncol Hematol. 2023;192:104187.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"1","key":"4249_CR5","doi-asserted-by":"publisher","first-page":"5350","DOI":"10.1038\/s41467-022-33093-3","volume":"13","author":"MDM Uddin","year":"2022","unstructured":"Uddin MDM, Nguyen NQH, Yu B, Brody JA, Pampana A, Nakao T, et al. Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease. Nat Commun. 2022;13(1):5350.","journal-title":"Nat Commun"},{"issue":"5","key":"4249_CR6","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1002\/ana.26754","volume":"94","author":"EJ Lee","year":"2023","unstructured":"Lee EJ, An HY, Lim J, Park KI, Choi SY, Jeong HY, et al. Clonal hematopoiesis and acute ischemic stroke outcomes. Ann Neurol. 2023;94(5):836\u201347.","journal-title":"Ann Neurol"},{"issue":"1","key":"4249_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79748-7","volume":"14","author":"E Gelli","year":"2024","unstructured":"Gelli E, Martinuzzi C, Soncini D, Conticello C, Ladisa F, Giorgetti G, et al. Clonal hematopoiesis impacts frailty in newly diagnosed multiple myeloma patients: a retrospective multicenter analysis. Sci Rep. 2024;14(1):29394.","journal-title":"Sci Rep"},{"issue":"7","key":"4249_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00706-5","volume":"12","author":"MF Gagnon","year":"2022","unstructured":"Gagnon MF, Tian S, Geyer S, Sharma N, Vachon CM, Kusne Y, et al. Distribution of clonal hematopoiesis of indeterminate potential (CHIP) is not associated with race in patients with plasma cell neoplasms. Blood Cancer J. 2022;12(7):112.","journal-title":"Blood Cancer J"},{"issue":"1","key":"4249_CR9","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1038\/s41467-020-16805-5","volume":"11","author":"TH Mouhieddine","year":"2020","unstructured":"Mouhieddine TH, Sperling AS, Redd R, Park J, Leventhal M, Gibson CJ, et al. Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant. Nat Commun. 2020;11(1):2996.","journal-title":"Nat Commun"},{"issue":"5","key":"4249_CR10","doi-asserted-by":"publisher","first-page":"96","DOI":"10.21037\/atm-23-1945","volume":"12","author":"L Saba","year":"2024","unstructured":"Saba L, Nasr L, Manrique-Succar J, Diacovo J, Chaulagain C. How we manage multiple myeloma with clonal hematopoiesis of indeterminate potential (CHIP): a case report. Ann Transl Med. 2024;12(5):96.","journal-title":"Ann Transl Med"},{"issue":"10297","key":"4249_CR11","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","volume":"398","author":"JG Berdeja","year":"2021","unstructured":"Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b\/2 open-label study. Lancet. 2021;398(10297):314\u201324.","journal-title":"Lancet"},{"issue":"25","key":"4249_CR12","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.1200\/JCO-25-00760","volume":"43","author":"S Jagannath","year":"2025","unstructured":"Jagannath S, Martin TG, Lin Y, Cohen AD, Raje N, Htut M, et al. Long-term (>\/=5-year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed\/refractory multiple myeloma. J Clin Oncol. 2025;43(25):2766\u201371.","journal-title":"J Clin Oncol"},{"issue":"4","key":"4249_CR13","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1056\/NEJMoa2303379","volume":"389","author":"J San-Miguel","year":"2023","unstructured":"San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335\u201347.","journal-title":"N Engl J Med"},{"key":"4249_CR14","doi-asserted-by":"crossref","unstructured":"Mateos MV, Dhakal B, Touzeau C, Leleu X, WCJ van de Donk N, Sidana S, et al. Overall Survival With Ciltacabtagene Autoleucel Versus Standard of Care in Lenalidomide-Refractory Multiple Myeloma: Phase 3 CARTITUDE-4 Study Update. 9\/25\/24\u20139\/28\/24; 21st International Myeloma Society Meeting2024.","DOI":"10.1016\/S2152-2650(24)02346-2"},{"issue":"15","key":"4249_CR15","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1182\/bloodadvances.2021004554","volume":"5","author":"PG Miller","year":"2021","unstructured":"Miller PG, Sperling AS, Brea EJ, Leick MB, Fell GG, Jan M, et al. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. Blood Adv. 2021;5(15):2982\u20136.","journal-title":"Blood Adv"},{"issue":"6","key":"4249_CR16","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1182\/bloodadvances.2021005747","volume":"6","author":"R Teipel","year":"2022","unstructured":"Teipel R, Kroschinsky F, Kramer M, Kretschmann T, Egger-Heidrich K, Kruger T, et al. Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment. Blood Adv. 2022;6(6):1941\u20136.","journal-title":"Blood Adv"},{"issue":"24","key":"4249_CR17","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1200\/JCO-24-01893","volume":"43","author":"H Avet-Loiseau","year":"2025","unstructured":"Avet-Loiseau H, Davies FE, Samur MK, Corre J, D\u2019Agostino M, Kaiser MF, et al. International myeloma society\/international myeloma working group consensus recommendations on the definition of high-risk multiple myeloma. J Clin Oncol. 2025;43(24):2739\u201351.","journal-title":"J Clin Oncol"},{"key":"4249_CR18","doi-asserted-by":"publisher","first-page":"7085","DOI":"10.1182\/blood-2024-201606","volume":"144","author":"M Delforge","year":"2024","unstructured":"Delforge M, Mateos MV, Carlson K, Qi K, Mendes J, Lee S, et al. Efficacy of Carvykti in Cartitude-4 versus alternative treatments from daratumumab clinical trials for the treatment of patients with lenalidomide-refractory multiple myeloma. Blood. 2024;144:7085.","journal-title":"Blood"},{"key":"4249_CR19","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1182\/blood-2024-201533","volume":"144","author":"AOR Popat","year":"2024","unstructured":"Popat AOR, Cavo M, Karlin L, Mazza IA, Roeloffzen W, Jin Kim S, et al. Ciltacabtagene Autoleucel (Cilta-cel) Vs Standard of Care (SoC) in Patients with Lenalidomide (Len)-Refractory Multiple Myeloma (MM) after 1\u20133 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 Cartitude-4 Trial. Blood. 2024;144:1032.","journal-title":"Blood"},{"issue":"12","key":"4249_CR20","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1182\/bloodadvances.2025015981","volume":"9","author":"JN Gustine","year":"2025","unstructured":"Gustine JN, Branagan AR, Cirstea DD, Rexha F, Han R, Yee AJ, et al. Impact of clonal hematopoiesis on clinical outcomes to BCMA CAR-T in multiple myeloma. Blood Adv. 2025;9(12):3026\u201330.","journal-title":"Blood Adv"},{"issue":"14","key":"4249_CR21","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1200\/JCO.2016.71.6712","volume":"35","author":"CJ Gibson","year":"2017","unstructured":"Gibson CJ, Lindsley RC, Tchekmedyian V, Mar BG, Shi J, Jaiswal S, et al. Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma. J Clin Oncol. 2017;35(14):1598\u2013605.","journal-title":"J Clin Oncol"},{"issue":"16","key":"4249_CR22","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1182\/bloodadvances.2018024729","volume":"3","author":"EK Cook","year":"2019","unstructured":"Cook EK, Izukawa T, Young S, Rosen G, Jamali M, Zhang L, et al. Comorbid and inflammatory characteristics of genetic subtypes of clonal hematopoiesis. Blood Adv. 2019;3(16):2482\u20136.","journal-title":"Blood Adv"},{"key":"4249_CR23","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.stem.2018.10.013","volume":"23","author":"Z Cai","year":"2018","unstructured":"Cai Z. Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis. Cell Stem Cell. 2018;23:833\u201349.","journal-title":"Cell Stem Cell"},{"issue":"6","key":"4249_CR24","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","volume":"24","author":"T Giavridis","year":"2018","unstructured":"Giavridis T, van der Stegen SJC, Eyquem J, Hamieh M, Piersigilli A, Sadelain M. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med. 2018;24(6):731\u20138.","journal-title":"Nat Med"},{"issue":"21","key":"4249_CR25","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1182\/blood-2017-06-793141","volume":"130","author":"KA Hay","year":"2017","unstructured":"Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017;130(21):2295\u2013306.","journal-title":"Blood"},{"key":"4249_CR26","doi-asserted-by":"crossref","unstructured":"al ADKe. Delayed Neurotoxicity after CAR-T in Multiple Myeloma: Results from a Global IMWG Registry. Blood. 2024;144:4758\u201360.","DOI":"10.1182\/blood-2024-201783"},{"issue":"2","key":"4249_CR27","first-page":"S215","volume":"31","author":"J Turner","year":"2025","unstructured":"Turner J, Forsberg PA, Nicholson S, Schade H, Matous J, Gregory TK. Prophylactic dexamethasone rescues unrestrained lymphocyte expansion in anti-BCMA chimeric antigen receptor T cell therapy in multiple myeloma. Transpl Cell Ther Off Publ Am Soc Transpl Cell Ther. 2025;31(2):S215\u20136.","journal-title":"Transpl Cell Ther Off Publ Am Soc Transpl Cell Ther"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04249-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04249-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04249-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:53:24Z","timestamp":1793282004000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04249-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["4249"],"URL":"https:\/\/doi.org\/10.1007\/s12185-026-04249-4","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]},"assertion":[{"value":"14 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ben Puliafito acts as a consultant for Sanofi and participates on the Advisory Board\/Data Safety Monitoring Board for Legend Biotech. John Timmerman has clinical research funding from Merck, Kite\/Gilead, Regeneron, and runs a CancerNetwork educational session. Sarah Larson received grants from BMS, Janssen, Kite, Pfizer, Regeneron; obtains consulting fees from BMS and Janssen; payments\/honoraria for Regeneron; and has stock with TORL biotherapeutics.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in accordance with the Declaration of Helsinki and ethical guidelines. The study protocol was approved by the institutional review boards.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}