TY - JOUR
T1 - Postibrutinib outcomes in patients with mantle cell lymphoma
AU - Martin, Peter
AU - Maddocks, Kami
AU - Leonard, John P.
AU - Ruan, Jia
AU - Goy, Andre
AU - Wagner-Johnston, Nina
AU - Rule, Simon
AU - Advani, Ranjana
AU - Iberri, David
AU - Phillips, Tycel
AU - Spurgeon, Stephen
AU - Kozin, Eliana
AU - Noto, Katherine
AU - Chen, Zhengming
AU - Jurczak, Wojciech
AU - Auer, Rebecca
AU - Chmielowska, Ewa
AU - Stilgenbauer, Stephan
AU - Bloehdorn, Johannes
AU - Portell, Craig
AU - Williams, Michael E.
AU - Dreyling, Martin
AU - Barr, Paul M.
AU - Chen-Kiang, Selina
AU - DiLiberto, Maurizio
AU - Furman, Richard R.
AU - Blum, Kristie A.
N1 - Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/3/24
Y1 - 2016/3/24
N2 - Despite unprecedented clinical activity inmantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients withMCLwho experienced disease progressionwhile receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 12 had a Ki67 >30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% confidence interval [CI], 1.6-4.9). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment after ibrutinib.
AB - Despite unprecedented clinical activity inmantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients withMCLwho experienced disease progressionwhile receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 12 had a Ki67 >30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% confidence interval [CI], 1.6-4.9). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment after ibrutinib.
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UR - http://www.scopus.com/inward/citedby.url?scp=84962325088&partnerID=8YFLogxK
U2 - 10.1182/blood-2015-10-673145
DO - 10.1182/blood-2015-10-673145
M3 - Article
C2 - 26764355
AN - SCOPUS:84962325088
SN - 0006-4971
VL - 127
SP - 1559
EP - 1563
JO - Blood
JF - Blood
IS - 12
ER -