Clinical Features and Outcomes of Therapy-Related Myeloid Neoplasms After CAR T-Cell Therapy

Therapy-related myeloid neoplasms (t-MN) after chimeric antigen receptor (CAR) T-cell therapy occur with short latency, but whether they carry an independent survival disadvantage is unclear. We assembled a multicenter retrospective cohort of 399 adults with t-MN after CAR T-cell therapy (n=56), autologous hematopoietic cell transplantation (auto-HCT; n=98), or standard chemotherapy/radiation (n=245), and constructed a nearest-neighbor latency-matched cohort (n=220). Median latency was 15.2 months for post-CAR-T versus 38.0 and 30.0 months for post-auto-HCT and standard therapy (p<0.001). In the matched cohort, median overall survival (OS) was 9.1 months for post-CAR-T versus 16.9 and 18.7 months for post-auto-HCT and standard therapy (p=0.013). In multivariable Cox models, the hazard ratio for overall mortality was 1.98 (95% CI 1.33-2.94) for post-CAR-T and 0.99 (95% CI 0.74-1.32) for post-auto-HCT, each relative to standard therapy; The post-CAR-T estimate was 1.85 (95% CI 1.21-2.82) after adjustment for TP53 status and 2.15 (95% CI 1.23-3.76) in an era-restricted cohort with near-complete molecular data. TP53 variant allele frequency independently predicted OS (HR 1.14 per 10% increment, 95% CI 1.03-1.26). The hazard ratio for allogeneic HCT, modeled as a time-varying covariate, was 0.74 (95% CI 0.52-1.06). Post-CAR-T t-MN carries an independent survival disadvantage not explained by TP53 clone burden; allogeneic HCT remains the only potentially curative option.

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Publication Details

Journal
Blood Advances
Published
2026-10-07
DOI
https://doi.org/10.1182/bloodadvances.2026021831
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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article

Clinical Features and Outcomes of Therapy-Related Myeloid Neoplasms After CAR T-Cell Therapy

Michael David Jain, Jongphil Kim, Rami S. Komrokji, Javier Delgado et al.
Blood Advances
Acute Myeloid Leukemia Research
article

Clinical Features and Outcomes of Therapy-Related Myeloid Neoplasms After CAR T-Cell Therapy

Michael David Jain, Jongphil Kim, Rami S. Komrokji, Javier Delgado, Claire Roddie, Saurabh Dahiya, Maeve A O'Reilly, Alaa Ali, David Andrew Sallman, Gloria Iacoboni, Jay Y. Spiegel, Eric Padron, Zhuoer Xie, Kai Rejeski, Showkat Hamid, Kai Rejeski, Jaime Roman Diaz, Zachary Thompson, Francesca Sillito, Ana Benzaquen, Pere Barba, Frederick L Locke, Najla Al-Ali, Peter Cheng
article en

Abstract

Therapy-related myeloid neoplasms (t-MN) after chimeric antigen receptor (CAR) T-cell therapy occur with short latency, but whether they carry an independent survival disadvantage is unclear. We assembled a multicenter retrospective cohort of 399 adults with t-MN after CAR T-cell therapy (n=56), autologous hematopoietic cell transplantation (auto-HCT; n=98), or standard chemotherapy/radiation (n=245), and constructed a nearest-neighbor latency-matched cohort (n=220). Median latency was 15.2 months for post-CAR-T versus 38.0 and 30.0 months for post-auto-HCT and standard therapy (p<0.001). In the matched cohort, median overall survival (OS) was 9.1 months for post-CAR-T versus 16.9 and 18.7 months for post-auto-HCT and standard therapy (p=0.013). In multivariable Cox models, the hazard ratio for overall mortality was 1.98 (95% CI 1.33-2.94) for post-CAR-T and 0.99 (95% CI 0.74-1.32) for post-auto-HCT, each relative to standard therapy; The post-CAR-T estimate was 1.85 (95% CI 1.21-2.82) after adjustment for TP53 status and 2.15 (95% CI 1.23-3.76) in an era-restricted cohort with near-complete molecular data. TP53 variant allele frequency independently predicted OS (HR 1.14 per 10% increment, 95% CI 1.03-1.26). The hazard ratio for allogeneic HCT, modeled as a time-varying covariate, was 0.74 (95% CI 0.52-1.06). Post-CAR-T t-MN carries an independent survival disadvantage not explained by TP53 clone burden; allogeneic HCT remains the only potentially curative option.

Blood Advances
University College Hospital (GB), Memorial Sloan Kettering Cancer Center (US), LMU Klinikum (DE), Moffitt Cancer Center (US), Hospital Clínico Universitario de Valencia (ES), Vall d'Hebron Hospital Universitari (ES), Instituto de Biomedicina de Sevilla (ES), Hospital Universitario Virgen del Rocío (ES), Sylvester Comprehensive Cancer Center (US), Vall d'Hebron Institute of Oncology (ES), University College London (GB), Ludwig-Maximilians-Universität München (DE), Stanford University (US)
Openalex Percentile: Top 12%
Acute Myeloid Leukemia Research
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