β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

Autor:	Thompson, Philip A., O'Brien, Susan M., Xiao, Lianchun, Wang, Xuemei, Burger, Jan A., Jain, Nitin, Ferrajoli, Alessandra, Estrov, Zeev, Keating, Michael J., Wierda, William G.
Předmět:	MICROGLOBULINS LEUKEMIA RITUXIMAB CYCLOPHOSPHAMIDE FLUDARABINE ANTINEOPLASTIC agents CARCINOGENESIS ANTIMETABOLITES ANTIVIRAL agents BLOOD proteins BONE marrow CHROMOSOMES CHRONIC lymphocytic leukemia COMPARATIVE studies GLOBULINS HETEROCYCLIC compounds IMMUNOGLOBULINS LONGITUDINAL method RESEARCH methodology MEDICAL cooperation PROGNOSIS RESEARCH RESEARCH funding TRANSFERASES EVALUATION research TREATMENT effectiveness PROPORTIONAL hazards models RETROSPECTIVE studies CASE-control method
Zdroj:	Cancer (0008543X); Feb2016, Vol. 122 Issue 4, p565-573, 9p
Abstrakt:	Background: A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date.Methods: The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes.Results: B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]).Conclusions: Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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