Myeloid neoplasms (TMNs), such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are an important cause of non-relapse mortality after CAR T-cell therapy. It is not known whether the characteristics and outcomes of TMNs after CAR T-cell therapy differ from those of TMNs occurring after other types of treatment.
We collected a multicenter, international cohort of 51 patients diagnosed with MDS (n=36) or AML (n=15) after CAR T-cell therapy for lymphoma or myeloma. Data was gathered on baseline characteristics, disease type, exposure to chemotherapy, radiation exposure, survival, disease risk, and molecular profiles. The characteristics and mutational profiles of this cohort (CAR T) were compared to historical single-institution cohorts of TMN occurring after autologous stem cell transplant (AUTO, n=96) or other standard anti-cancer therapies (STD=244) such as chemotherapy and/or radiation.
The baseline characteristics for the three cohorts of TMN (post-CAR T, post-AUTO, and post-STD) were similar in terms of age, sex, and ethnicity. The time to onset of TMN was significantly shorter post-CAR T than the other cohorts (CAR T 20 months, AUTO 63.6 months, STD 62.1 months, p<0.001). No significant differences between cohorts were noted in terms of baseline IPSS-R risk categories or the frequency of any specific somatic myeloid mutation. TP53 mutations were the most common somatic mutation in all three cohorts (CAR T 47%, AUTO 47%, STD 39%) but were not more frequent in the CAR T cell cohort. Overall survival from the time of TMN diagnosis was significantly shorter in the post-CAR T cell therapy cohort (median OS months for CAR T=9.2, AUTO=24.4, STD=19.2; log-rank p=0.005).
The time to onset of TMNs is shorter post-CAR T cell therapy compared to post-AUTO or post-other STD cancer therapies. TMNs occurring after CAR T have a similar cytogenetic risk and mutational profile compared to other TMNs, but shorter overall survival from the time of TMN diagnosis. Additional work is needed to understand risk factors, the shorter time of onset, and the particularly poor prognosis of patients experiencing TMN after CAR T cell therapies.
Dahiya:Adaptive Biotechnologies: Consultancy; Bristol Myers Squibb: Consultancy; Kite: Consultancy, Research Funding; Kite-Pharma-Gilead: Consultancy, Research Funding. Sillito:Kite, Gilead: Honoraria. O'Reilly:Autolus: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria. Rejeski:kite/gilead: Consultancy, Honoraria, Other: Travel support, Research Funding; Pierre-Fabre: Other: Travel support; novartis: Honoraria; BMS/celgene: Consultancy, Honoraria. Buecklein:Janssen: Research Funding; Pfizer: Consultancy, Honoraria; Pierre Fabre: Consultancy; Otsuka: Consultancy; BMS: Research Funding; Takeda: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Subklewe:Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Roche, Seagen, Takeda: Research Funding; AbbVie, Amgen, Autolus, AvenCell, BMS, CanCell Therapeutics, Genmab US, Gilead, Ichnos Sciences, Incyte Biosciences, Interius BioTherapeutics, Janssen, Miltenyi Biomedicine, Molecular Partners, Nektar Therapeutics, Novartis, Orbital Therapeutics, Pfizer,: Honoraria; AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche, Springer Healthcare: Speakers Bureau. Iacoboni:Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis: Consultancy; Autolus: Consultancy; Novartis: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; BMS: Consultancy, Honoraria; AstraZeneca: Honoraria, Other: Travel support; AbbVie: Honoraria, Other: Travel Support; AbbVie, AstraZeneca, Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis, Lilly and Sandoz: Honoraria; Miltenyi: Consultancy, Honoraria; AbbVie, AstraZeneca, Kite/Gilead, Miltenyi: Other: Travel support. Roddie:Kite Gilead: Consultancy, Speakers Bureau; Autolus Tx: Consultancy; novartis: Honoraria; Johnson&Johnson: Honoraria; Bristol Myers: Honoraria. Locke:Cowen: Consultancy; Society for Immunotherapy of Cancer: Honoraria; Iovance: Consultancy; Gerson Lehrman Group (GLG): Consultancy; Clinical Care Options Oncology: Honoraria; EcoR1: Consultancy; Kite, a Gilead Company: Consultancy, Other: institutional, travel, accomodation, expenses, Research Funding; Aptitude Health: Honoraria; Communications CARE Education: Honoraria; Legend Biotech: Consultancy; Novartis: Consultancy, Research Funding; Janssen: Consultancy; 2SeventyBio: Other: Institutional, Research Funding; National Cancer Institute: Other: Institutional, Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Other: Institutional, Research Funding; Imedex: Honoraria; Moffitt Cancer Center: Patents & Royalties; Allogene: Other: Institutional, Research Funding; CERo Therapeutics: Research Funding; Caribou: Consultancy; Calibr: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; A2: Consultancy; Amgen: Consultancy; Bluebird Bio: Consultancy; BioPharma Communications CARE Education: Honoraria; American Society of Hematology: Honoraria, Other: travel, accomodation, expenses; Sana: Consultancy; Umoja: Consultancy; Pfizer: Consultancy. Komrokji:PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Keros: Membership on an entity's Board of Directors or advisory committees; Taiho: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servio: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servio: Honoraria; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jain:Myeloid Therapeutics: Consultancy; Incyte: Research Funding; Loxo: Research Funding; Kite/Gilead: Consultancy, Research Funding.
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