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Chronic lymphocytic leukemia

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 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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Acknowledgements

This was supported, in part, by the MD Anderson Cancer Center Support Grant P30 CA016672. The authors would like to acknowledge the contributions of the late Ms. Susan Lerner and Mark Hess in the maintenance of the CLL database at the MD Anderson.

Author contributions

P.A.T. collected and analyzed data, provided clinical care to patients and wrote the paper. C.B.P. performed statistical analysis and co-wrote the paper. P.S. collected and analyzed data and co-wrote the paper. J.J. collected and analyzed flow cytometry data and co-wrote the paper. M.J.K., S.M.O., A.F., J.A.B., Z.E., N.J., T.M.K., G.B., C.D., N.D., and E.J. provided clinical care to patients and co-wrote the paper. W.G.W. designed and implemented the study, analyzed data, provided clinical care to patients, and wrote the paper. All authors reviewed and authorized the final version.

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Correspondence to William G. Wierda.

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Conflict of interest

P.A.T. has served as a consultant for Pharmacyclics and AbbVie and has received research funding from AbbVie. M.J.K. has served as a paid consultant for Roche/Genentech and Pharmacyclics. S.M.O. has served as a consultant for Janssen Oncology and AbbVie and has received research support from Pharmacyclics. J.A.B. has served as a consultant for Pharmacyclics and Janssen and has received research funding from Pharmacyclics. N.J. has served as a consultant for Pharmacyclics and has received research funding from Pharmacyclics and AbbVie. C.D. has received speaking fees from AbbVie. W.G.W. has served as a consultant for Pharmacyclics, AbbVie, and Roche/Genentech and has received research funding from AbbVie, Pharmacyclics, and Genentech. The remaining authors declare that they have no conflict of interest.

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Thompson, P.A., Peterson, C.B., Strati, P. et al. Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies. Leukemia 32, 2388–2398 (2018). https://doi.org/10.1038/s41375-018-0132-y

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