In an analysis reported in a research letter in JAMA Oncology, Gurney et al identified factors associated with an increased risk of myeloid neoplasms after chimeric antigen receptor (CAR) T-cell therapy.
Study Details
Investigators identified adults who received CAR T-cell therapy between June 2016 and December 2021 for lymphoproliferative disease or multiple myeloma at Mayo Clinic sites in Minnesota, Florida, and Arizona and later developed myeloid neoplasms. Cases were compared with control patients who did not develop myeloid neoplasms.
Key Findings
Median follow-up was 14 months (interquartile range [IQR] = 6–23 months). A total of 20 patients developed myeloid neoplasms at a median of 10 months (IQR = 5–18 months) after CAR T-cell infusion. A total of 220 patients who did not develop myeloid neoplasms constituted the control group. The estimated cumulative incidence of myeloid neoplasms was 4%, 6%, and 9% at 1, 2, and 3 years, respectively.
Clonal hematopoiesis was observed in 7 (64%) of 11 evaluable cases, involving mainly TP53 and PPM1D.
On univariate analysis, factors associated with increased risk of myeloid neoplasms were older age, lower hemoglobin level, and lower platelet count. A multivariate model consisting of age ≥ 65 years and platelet count ≤ 140,000/μL yielded the highest concordance index (0.776). On this model, estimated myeloid neoplasms rates were 4 per 100 person-years with one factor and 27 per 100 person-years with two factors (P < .001). No myeloid neoplasms were observed in patients with no factors at 80 person-years of follow-up.
The investigators stated, “Intuitive baseline factors of age and thrombocytopenia can stratify myeloid neoplasm risks occurring in patients after CAR T-cell therapy, regardless of clonal hematopoiesis, supporting counseling and guiding surveillance strategies.”
Mithun Vinod Shah, MD, PhD, of the Division of Hematology, Mayo Clinic, Rochester, Minnesota, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by a K2R Pipeline Award from the Mayo Clinic, a grant from the National Center for Advancing Translational Sciences, and others. For full disclosures of the study authors, visit jamanetwork.com.
