ALL-175: High CD38 and CD58 Expression on Leukemia Cells, Forming MRD Population, Dramatically Decreases Relapse-Free Survival in B-ALL Patients Enrolled in RALL-2016 Study

Context: It is well known that measurable residual disease (MRD) has a significant prognostic impact in patients with acute leukemia. However, the effect of the immunophenotype of MRD cells has not been studied yet. Objective: The aim of the study was to assess the significance of CD38 and CD58 expression for relapse-free survival (RFS) in B-ALL patients. Design: This study included data from 2016 to 2020 for patients enrolled in the Russian multicenter study RALL-2016 (NCT03462095). MRD was assessed in the bone marrow at the end of induction (day +70) in patients who achieved a complete remission. Patients and Methods: The RALL-2016 study included 207 adult patients. The MRD was assessed in 150 patients (80 B-ALL patients and 70 T-ALL patients). Analysis of MRD was performed by 6- or 10-color flow cytometry. The sensitivity was at least 0.01%. CD19, CD34, CD10, CD20, CD38, CD45, and CD58 were analyzed to detect MRD. The main immunophenotypic features of B-ALL blasts are low CD38 expression and high CD58 expression. CD38 expression in MRD cells was considered low if it was lower than that on normal B-cell progenitors. CD58 expression was considered high if it was equal to or higher than that on plasma cells. The RFS was estimated with the Kaplan–Meier method, and comparisons were assessed using the log-rank test. Results: Among B-ALL patients, 48 (60%) patients were MRD-negative, and 32 (40%) patients remained MRD-positive at the end of induction. The duration of RFS was lower in MRD-positive patients (median 29.5 months vs median undefined, p=0.004). Among MRD cells, high CD38 expression was found in 8 patients, and 7 (87.5%) of these relapsed or died. RFS was shorter in CD38-high-MRD patients than in CD38-low-MRD (median 5.2 months vs median undefined, p<0.001). RFS in CD58-high-MRD was also shorter (medians 9.7 vs 34.7 months, p<0.001). Conclusion: MRD at the end of induction was confirmed as an important prognostic factor in the RALL-2016 study. However, immunophenotyping residual blasts could improve the prognostic impact of MRD. High expression of CD58 and CD38 on MRD cells dramatically decreases the duration of RFS in B-ALL patients. It is well known that measurable residual disease (MRD) has a significant prognostic impact in patients with acute leukemia. However, the effect of the immunophenotype of MRD cells has not been studied yet. The aim of the study was to assess the significance of CD38 and CD58 expression for relapse-free survival (RFS) in B-ALL patients. This study included data from 2016 to 2020 for patients enrolled in the Russian multicenter study RALL-2016 (NCT03462095). MRD was assessed in the bone marrow at the end of induction (day +70) in patients who achieved a complete remission. The RALL-2016 study included 207 adult patients. The MRD was assessed in 150 patients (80 B-ALL patients and 70 T-ALL patients). Analysis of MRD was performed by 6- or 10-color flow cytometry. The sensitivity was at least 0.01%. CD19, CD34, CD10, CD20, CD38, CD45, and CD58 were analyzed to detect MRD. The main immunophenotypic features of B-ALL blasts are low CD38 expression and high CD58 expression. CD38 expression in MRD cells was considered low if it was lower than that on normal B-cell progenitors. CD58 expression was considered high if it was equal to or higher than that on plasma cells. The RFS was estimated with the Kaplan–Meier method, and comparisons were assessed using the log-rank test. Among B-ALL patients, 48 (60%) patients were MRD-negative, and 32 (40%) patients remained MRD-positive at the end of induction. The duration of RFS was lower in MRD-positive patients (median 29.5 months vs median undefined, p=0.004). Among MRD cells, high CD38 expression was found in 8 patients, and 7 (87.5%) of these relapsed or died. RFS was shorter in CD38-high-MRD patients than in CD38-low-MRD (median 5.2 months vs median undefined, p<0.001). RFS in CD58-high-MRD was also shorter (medians 9.7 vs 34.7 months, p<0.001). MRD at the end of induction was confirmed as an important prognostic factor in the RALL-2016 study. However, immunophenotyping residual blasts could improve the prognostic impact of MRD. High expression of CD58 and CD38 on MRD cells dramatically decreases the duration of RFS in B-ALL patients.