TY - JOUR
T1 - Long-term outcomes and mutation profiling of patients with mantle cell lymphoma (MCL) who discontinued ibrutinib
AU - Jain, Preetesh
AU - Kanagal-Shamanna, Rashmi
AU - Zhang, Shaojun
AU - Ahmed, Makhdum
AU - Ghorab, Ahmad
AU - Zhang, Liang
AU - Ok, Chi Young
AU - Li, Shaoying
AU - Hagemeister, Frederick
AU - Zeng, Dongfeng
AU - Gong, Tiejun
AU - Chen, Wendy
AU - Badillo, Maria
AU - Nomie, Krystle
AU - Fayad, Luis
AU - Medeiros, Leonard J.
AU - Neelapu, Sattva
AU - Fowler, Nathan
AU - Romaguera, Jorge
AU - Champlin, Richard
AU - Wang, Linghua
AU - Wang, Michael L.
N1 - Publisher Copyright:
© 2018 British Society for Haematology and John Wiley & Sons Ltd
PY - 2018/11
Y1 - 2018/11
N2 - Long term outcomes and mutations in patients with mantle cell lymphoma (MCL) who discontinued ibrutinib have not been described. Using deep targeted next generation sequencing, we performed somatic mutation profiling from 15 MCL patients (including 5 patients with paired samples; before and after progression on ibrutinib). We identified 80 patients with MCL who discontinued ibrutinib therapy for various reasons. Median follow-up after ibrutinib discontinuation was 38 months. The median duration on ibrutinib was 7·6 months. Forty-one (51%) patients discontinued ibrutinib due to disease progression/transformation, 20 (25%) for intolerance, 7 (9%) due to patient choice, 5 (6%) for stem cell transplant, 4 (5%) due to second cancers and 3 (4%) other causes. The median survival after ibrutinib was 10 and 6 months for disease progression and transformation, respectively, and 25 months for patients with ibrutinib intolerance. Overall, BTK mutations were observed in 17% patients after progression on ibrutinib. Notably, TP53 alterations were observed after progression in 75% patients. Among the 4 patients with blastoid transformation, 3 (75%) had NSD2 mutations (co-existing with TP53). Ibrutinib-refractory MCL patients had a short survival. Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.
AB - Long term outcomes and mutations in patients with mantle cell lymphoma (MCL) who discontinued ibrutinib have not been described. Using deep targeted next generation sequencing, we performed somatic mutation profiling from 15 MCL patients (including 5 patients with paired samples; before and after progression on ibrutinib). We identified 80 patients with MCL who discontinued ibrutinib therapy for various reasons. Median follow-up after ibrutinib discontinuation was 38 months. The median duration on ibrutinib was 7·6 months. Forty-one (51%) patients discontinued ibrutinib due to disease progression/transformation, 20 (25%) for intolerance, 7 (9%) due to patient choice, 5 (6%) for stem cell transplant, 4 (5%) due to second cancers and 3 (4%) other causes. The median survival after ibrutinib was 10 and 6 months for disease progression and transformation, respectively, and 25 months for patients with ibrutinib intolerance. Overall, BTK mutations were observed in 17% patients after progression on ibrutinib. Notably, TP53 alterations were observed after progression in 75% patients. Among the 4 patients with blastoid transformation, 3 (75%) had NSD2 mutations (co-existing with TP53). Ibrutinib-refractory MCL patients had a short survival. Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.
KW - BTK
KW - drug resistance
KW - ibrutinib
KW - mantle cell lymphoma (MCL)
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U2 - 10.1111/bjh.15567
DO - 10.1111/bjh.15567
M3 - Article
C2 - 30175400
AN - SCOPUS:85052811826
SN - 0007-1048
VL - 183
SP - 578
EP - 587
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -