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

Leukemia
Philip A ThompsonWilliam G Wierda

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 38 mo, 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 73 mo vs 41 mo, 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 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.

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Citations

Dec 7, 2018·Hematology·Nitin Jain
Jun 13, 2019·International Journal of Molecular Sciences·Ricardo SánchezJoaquín Martínez-López
Aug 29, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jennifer A Woyach
Apr 8, 2020·International Journal of Hematology·Junji Suzumiya, Jun Takizawa
Sep 27, 2019·Frontiers in Oncology·Ilaria Del GiudiceRobin Foà

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Methods Mentioned

BETA
biopsy

Clinical Trials Mentioned

NCT00759798
NCT02048813
NCT02950051

Software Mentioned

rpart
R

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