ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Clonal Hematopoiesis and Inflammation Predict Hematologic Toxicity and Secondary Myeloid Malignancies after B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-cell Therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.Human vaccines & immunotherapeutics · 2026Review
- Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications.International journal of laboratory hematology · 2026Review
- Plasticity under pressure: biology and detection of lineage switch in acute leukemia.Leukemia · 2026Review
- TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy.Leukemia · 2026Article
- Genomic features of clonal hematopoiesis-associated genes in primary and CAR T-cell-related secondary T-cell malignancies.Blood neoplasia · 2026Article
- Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen-Directed CAR T-Cell Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Flare of clonal hematopoiesis, TP53 expansion and prior melphalan drive post-CAR-T myeloid disorders in multiple myeloma.Leukemia · 2026Article
- Clonal hematopoiesis dynamics influences long-term outcomes of follicular lymphoma: Results from FIL FOLL12 trial.HemaSphere · 2026Article
- Counting the CHIPs: The High-Stakes Role of Clonal Hematopoiesis in Multiple Myeloma.Biomedicines · 2026Review
- Biomarker-empowered precision navigation of CAR-T cell therapy.Molecular cancer · 2026Review
- Pre-Infusion Host-Marrow Vulnerability in CD19- and BCMA-Directed CAR T-Cell Therapy: Clonal Hematopoiesis, Hematotoxicity, and Therapy-Related Myeloid Neoplasia.Cancer management and research · 2026Review
- Venetoclax combined with azacitidine in the treatment of secondary myelodysplastic syndrome following multiple myeloma: a case report and literature review.Frontiers in oncology · 2026Article
- Antibody-Drug Conjugates, T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What's the Current Status?Targeted oncology · 2026Review
- Risk Factors beyond Chemotherapy Exposure for Secondary Myeloid Neoplasms after Hematologic Cancers: A SEER-Based Study.Cancer research communications · 2025Article
- Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies?Journal of cancer research and clinical oncology · 2025Article
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20 authors.
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Abstract
purposeChimeric antigen receptor T cells (CAR-T) have demonstrated remarkable efficacy in multiple myeloma, but prolonged hematologic toxicity remains a common adverse event, and secondary myeloid malignancies are a significant safety concern. EXPERIMENTAL
designWe evaluated 213 patients with myeloma treated with B-cell maturation antigen-directed CAR-T at our center to characterize clinical, inflammatory, and myeloid clonal features associated with hematologic toxicity.
resultsPatients with persistent grade ≥3 neutropenia or thrombocytopenia at day 100 (19%) had shorter progression-free survival (P = 0.0003) and overall survival (P < 0.0001), and among those with continued remissions, 64% developed prolonged high-grade cytopenias beyond 1 year. Whereas baseline inflammation is a risk factor for hematologic toxicity, underlying clonal hematopoiesis (CH) modulated this risk, and the combination of CH and elevated ferritin was highly predictive of delayed recovery (adjusted HR, 0.38, P = 0.006). Serum cytokine analysis in patients with delayed myeloid recovery showed a signature of persistent inflammation and endothelial dysfunction. Finally, 9% developed secondary myeloid diseases, including 5% with high-grade myelodysplastic syndrome (MDS) requiring therapy, a median of 14.5 months after CAR-T. MDS was associated with clonal expansion of underlying TP53-mutated CH from a median variant allele frequency of 3.4% before CAR-T to 44.0%. Whereas patients with baseline TP53-mutated CH exhibited clonal evolution and a high incidence of MDS (67%), other CH mutations did not show similar expansion after CAR-T (P > 0.99).
conclusionsThis study underscores the impact of hematologic toxicity and CH on B-cell maturation antigen CAR-T outcomes and suggests a potential role of CAR-T in influencing TP53 clonal dynamics and myeloid disease development.
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