Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies

Abstract

Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end-of-therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10−4). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38mo, p<0.001). MRD level (≤1% vs. >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs. 9%, p<0.001). PFS was significantly longer for patients with MRD ≤1% vs. >1% after C3 (median 73mo vs 41mo, p<0.001), but similar for <0.01% vs. 0.01–1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.

High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

“…In addition, Thompson et al recently reported that undetectable MRD after course 3 of FCR predicted a greater likelihood of undetectable MRD at the end of therapy. 24…”

Minimal Residual Disease Monitoring with Next-Generation Sequencing Methodologies in Hematological Malignancies

“…All of these methods can provide information on MRD, which can help guide risk-adapted management and predict progression-free survival (PFS) and overall survival (OS) in patients. Accordingly, MRD is now routinely incorporated into clinical algorithms for several malignant hematologic diseases including MM [11], acute myeloid leukemia (AML) [12,13,14], ALL [15], and CLL [16,17].…”

Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia

“…Several studies have shown the survival benefit associated with MRD-negative status regardless of the treatment used to attain it [8,18]. Most data were derived from studies of chemoimmunotherapy, including several large phase 3 randomized studies (CLL8, CLL10, CLL11) [8,16,[19][20][21], as well as smaller studies in both first-line and the relapsed settings [22,23]. Since the initiation of the GIBB trial, the use of ibrutinib has emerged as a preferred first-line treatment in older CLL patients.…”