TY - JOUR
T1 - β2-microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia
AU - Thompson, Philip A.
AU - O'Brien, Susan M.
AU - Xiao, Lianchun
AU - Wang, Xuemei
AU - Burger, Jan A.
AU - Jain, Nitin
AU - Ferrajoli, Alessandra
AU - Estrov, Zeev
AU - Keating, Michael J.
AU - Wierda, William G.
N1 - Publisher Copyright:
© 2015 American Cancer Society.
PY - 2016/2/15
Y1 - 2016/2/15
N2 - 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.
AB - 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.
KW - BTK inhibitor
KW - chemoimmunotherapy
KW - chronic lymphocytic leukemia
KW - ibrutinib
KW - β-microglobulin
UR - http://www.scopus.com/inward/record.url?scp=84959113332&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959113332&partnerID=8YFLogxK
U2 - 10.1002/cncr.29794
DO - 10.1002/cncr.29794
M3 - Article
C2 - 26588193
AN - SCOPUS:84959113332
SN - 0008-543X
VL - 122
SP - 565
EP - 573
JO - Cancer
JF - Cancer
IS - 4
ER -