Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies. Issue 11 (November 2018)

• Record Type: Journal Article
• Authors: Thompson, Philip; Peterson, Christine; Strati, Paolo; Jorgensen, Jeff; Keating, Michael; O'Brien, Susan; Ferrajoli, Alessandra; Burger, Jan; Estrov, Zeev; Jain, Nitin; Kadia, Tapan; Borthakur, Gautam; DiNardo, Courtney; Daver, Naval; Jabbour, Elias; Wierda, William
• Is Part Of: Leukemia. Volume 32:Issue 11(2018)
• Page Start: 2388
• Page End: 2398
• Publication Date: 2018-11
• Subjects: Leukemia -- Periodicals; 616.99419
• DOI: 10.1038/s41375-018-0132-y
• Languages: English
• ISSNs: 0887-6924

Abstract

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.