CD72 as a complementary B‐lineage marker for longitudinal measurable residual disease surveillance after CD19 CAR ‐T therapy in R/R B‐ ALL Man Chen, Jing Zhou, Wei Zhao, Jing Long, Minjing Fu, Xian Zhang, Yi Li, Gailing Zhang, Hui Wang

Abstract

This study aimed to evaluate the feasibility of CD72 as a complementary CD19‐independent B‐lineage gating marker for longitudinal measurable residual disease (MRD) surveillance in relapsed/refractory B‐cell acute lymphoblastic leukemia (R/R B‐ALL) following CD19 CAR‐T therapy. Correlation analyses were performed in 66 B‐ALL samples to compare MRD detection using CD72, CD19, and cytoplasmic CD79a. CD72 expression specificity was further evaluated in 129 leukemia patients. In addition, 129 patients with R/R B‐ALL treated with autologous CD19 CAR‐T therapy in registered clinical trials ( ChiCTR‐IIh‐16008711; NCT03173417 ) between January 2021 and December 2022 were retrospectively analyzed, with follow‐up continued until January 2025. CD72 gating showed excellent concordance with both CD19‐ and cCD79a‐based strategies for MRD assessment. CD72 expression demonstrated high specificity in B‐ALL, with a positivity rate of 95.77%, compared with 29.27% in AML and 23.53% in T‐ALL. All 129 heavily pretreated patients achieved MRD‐negative CR at day 28 after CAR‐T infusion and subsequently underwent allo‐HSCT, with a median interval of 54 days (range, 40–338). A total of 16 patients experienced MRD relapse during follow‐up, including four clinically confirmed CD19‐negative relapses that retained CD72 expression. Patients with pre–CAR‐T MRD ≤1% showed earlier B‐cell recovery than those with MRD >1% (median 30 [18–45] vs. 32 [26–79] days, p  = 0.028). The MRD ≤1% cohort demonstrated significantly improved 3‐year overall survival compared with the MRD >1% cohort (88.1% vs. 69.2%, p  = 0.014). The 3‐year cumulative incidence of MRD relapse was significantly lower in the MRD ≤1% cohort than in the MRD >1% cohort (3.96% vs. 17.95%, p  = 0.019), while non‐relapse mortality was also numerically lower in the MRD ≤1% cohort (5.92% vs. 17.95%, p  = 0.053). Multivariate analysis identified KMT2A rearrangement, IKZF1 mutation, TP53 mutation, and elevated pre–CAR‐T MRD as independent predictors of inferior outcomes. CD72 represents a feasible complementary B‐lineage marker for longitudinal MRD surveillance following CD19 CAR‐T therapy. Retention of CD72 expression in clinically confirmed CD19‐negative relapses supports its potential utility when CD19 expression is lost after targeted therapy.