Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.
BACKGROUND
Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported.


METHODS
Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed.


RESULTS
Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy.


CONCLUSIONS
Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Preetesh
P
Jain
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Philip A
PA
Thompson
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Michael
M
Keating
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Zeev
Z
Estrov
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Alessandra
A
Ferrajoli
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nitin
N
Jain
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Hagop
H
Kantarjian
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jan A
JA
Burger
Chao Family Comprehensive Cancer Center, University of California-Irvine, Orange, California.
Susan
http://orcid.org/0000-0003-3386-6540
S
O'Brien
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
William G
WG
Wierda
D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069340:Deprescriptions; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate
D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
Chronic lymphocytic leukemia (CLL); Richter transformation; ibrutinib; venetoclax