MRD assessment post-CAR-T predicts ALL allo-HSCT bridging

Applying multi-colour flow cytometry gating based on cytoplasmic (c)CD79a expression can effectively monitor minimal residual disease (MRD) after CD19 CAR-T therapy and predicts the prognosis of bridging to allogeneic haematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (R/R B-ALL).

Dr Hui Wang (Hebei Yanda Ludaopei Hospital, China) explained the need for alternative gating panels for MRD detection by flow cytometry in B-ALL cases receiving CD19 CAR-T treatment [1]. To this end, Dr Wang and her team assessed MRD in the bone marrow of 59 patients by flow cytometry who had been treated with anti-CD19 CAR-T therapy bridging to allo-HSCT from June 2016 to March 2017. Instead of gating for CD19 in combination with the standard B-ALL markers (CD38/CD10/CD34/CD19/CD13+33/CD20/CD45 and CD81/CD34/cCD79a/CD10/CD45), the researchers investigated the prognostic value of gating for cCD79a in combination with a modified panel (CD38/CD10/CD34/CD19/cCD79a/CD20/CD45 and CD81/CD34/cCD79a/CD10/CD45).

To first validate the new panel against the old, 10 normal control bone marrow samples and 10 B-ALL MRD-positive samples were analysed in parallel. The new panel highly correlated with the standard panel, in normal control (R²=0.992), and MRD-positive (R²=0.9975) samples. The researchers then applied the new panel before and after treatment with CD19 CAR-T therapy for all 59 cases with cCD79a gating.

The results indicated that the new panel was prognostic of anti-CD19 CAR-T therapy bridging to allo-HSCT. Before CD19 CAR-T treatment, MRD varied between 0.48% and 93.28% (median 8.31%). Most patients (n=51) achieved MRD-negative complete remission (CR) after CAR-T therapy, and received allo-HSCT at a median of 64 days later. The 8 patients who were MRD-positive or relapsed after CAR-T therapy received allo-HSCT at a median of 31 days later.

With a median follow-up of 24 months after allo-HSCT, 42/51 cases (82.35%) achieved undetectable MRD. MRD was detected in 3/51 patients (5.88%) in the period of 90 to 450 days (median 120 days), and the remaining patients were lost to follow-up. Of the 8 patients who received allo-HSCT while being MRD-positive, 3 (37.5%) achieved MRD-negative CR status within in 24 months; 1 additional patient (12.5%) became MRD-negative CR in 5 months. The other 4 (50%) remained MRD-positive with 0.0031% to 1.93% detectable disease, of whom 2 died from relapse.

1. Chen M, et al. Multicolor flow cytometry panel with CCD79A gating to detect minimal residual disease in patients with B-lymphoblastic leukemia/lymphoma post anti-CD19 CAR-T therapy bridging to allo-HSCT. EHA25 Virtual, 11-21 June 2020, Abstract S113.