CD20 expression dynamics in adult B-cell acute lymphoblastic leukemia and impact on anti-CD20 treatment.
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BACKGROUND: Baseline CD20 expression ≥ 20% in B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poorer outcomes, which improved after rituximab introduction into frontline therapy for CD20-positive cases. We investigated the clinical and biological significance of this threshold by monitoring early dynamics of CD20 expression. METHODS: In the GMALL 08/2013 trial, adults with B-ALL received a cyclophosphamide/dexamethasone prephase, followed by Induction and Consolidation I, which included four rituximab doses in BCR::ABL1-negative patients, irrespective of CD20 status. CD20 expression was measured by standardized multiparametric flow cytometry in 274 patients in bone marrow and blood at diagnosis and in blood after prephase. IG/TR based measurable residual disease (MRD) was correlated with baseline bone marrow or the highest CD20-positive blast percentage recorded throughout prephase. The historical GMALL 07/2003 cohort treated without rituximab served for comparison. RESULTS: Baseline CD20 expression was significantly higher in blood than in bone marrow and increased further during prephase. In paired baseline samples, 6/76 c-/pre-B ALL cases (7.9%) were CD20-negative by bone marrow (< 20%) but positive in blood. In paired blood samples, 14/106 patients crossed the 20% threshold after prephase (12/86 c-/pre-B ALL, 13.9% and 2/20 pro-B ALL, 10.0%). Among 182 BCR::ABL1-negative patients, highest recorded CD20 across all time points classified 76 (41.8%) as < 20% and 106 (58.2%) as ≥ 20%. Higher CD20 expression was associated with improved MRD response under rituximab. Among MRD-evaluable patients after Induction I (n = 161), molecular complete remission (MolCR) was achieved in 10.6% of patients with CD20 expression < 20% compared with 30.5% of those with CD20 expression ≥ 20%. After Consolidation I (n = 159), corresponding MolCR rates were 50.0% and 72.6%, respectively. Associations were weaker when only baseline CD20 bone marrow status was considered. No association with MRD response was observed in GMALL 07/2003 patients treated without rituximab, suggesting a treatment-driven effect in GMALL 08/2013. CONCLUSIONS: CD20 expression in adult B-ALL varies from diagnostic bone marrow to blood and post-prephase measurements. The highest recorded CD20% value better predicts early MRD responses under rituximab. Post-prephase CD20 reassessment in blood identifies additional patients with eligibility for rituximab. REGISTRY: ClinicalTrials.gov, TRN: NCT02881086 (2016-08-23); NCT00198991 (2005-09-12).