The Journal of the Arkansas Medical Society Med Journal Feb 2020_Final | Page 12

Case Study
by Shifang Wang, MD; Diana Abraham, MD; Sai Prasad Desikan, MD;
Jay Jeffrey, MD; Charles McClain,III, MD; Raman Desikan, MD
White River Health System (Batesville, Ark.)
Delayed Acute Pancreatitis Induced by Nilotinib in
a Patient With Chronic Myeloid Leukemia Attaining
Complete Molecular Response
Abstract
C
hronic myeloid leukemia (CML) is a my-
eloproliferative neoplasm characterized
by Philadelphia chromosome t (9:22)
(q34; q11) and driven by resultant fu-
sion product, (BCR-ABL1) a tyrosine kinase. In-
troduction of imatinib, a selective tyrosine kinase
inhibitor of BCR-ABL1, resulted in dramatic im-
provement in response and survival. 1,2 Nilotinib,
a second-generation tyrosine kinase inhibitor
that is more potent and specific for BCR-ABL, is
increasingly employed as front-line therapy and
associated with increased
and rapid response. 5,6 We
would like to report our
observation of delayed
onset acute pancreatitis
in a patient attaining com-
plete molecular response
(MR4.5)
upper quadrant and epigastric area, which had
acutely worsened over previous three to four
days. On evaluation, she had tenderness to pal-
pation in the epigastric region without guarding
or rebound tenderness. Vitals at presentation
showed a temperature of 97.4 F, heart rate of
80 bpm, blood pressure of 131/69, respiratory
rate of 18/min, and oxygen saturation of 95%
on room air. Chemistries were significant for an
amylase elevated at 154 U/L, lipase elevated at
1775 U/L, and a bilirubin at 1.4 mg/dl. Serum
triglyceride at presentation was 149mg/dl. CT
patient also denied alcohol and recreational drug
use. She did not report any abdominal trauma.
Review of drugs revealed nilotinib as probable
cause of drug-induced pancreatitis. Nilotinib was
discontinued. She improved significantly with
supportive care; on discharge after four days of
hospitalization, lipase level was down to 353U/L.
Due to complete molecular response to nilotinib
(MR4.5), she was observed closely without any
further therapy. Molecular remission has persist-
ed for over a year on close monitoring.
Discussion
Chronic Myelogenous Leu-
kemia (CML) is a myelopro-
liferative disorder character-
ized by the overproduction
of myeloid cells from unre-
strained expansion of my-
eloid pluripotent stem cells.
The characteristic abnormal-
ity results from reciprocal
Case Report
translocation of chromo-
A 78-year-old Caucasian
somes 9 and 22, resulting in
female was started on ni-
der9q+ and 22q-, called the
lotinib as front-line therapy
Philadelphia chromosome.
in 2013. She tolerated ni-
The resultant BCR-ABL1
lotinib therapy other than
fusion protein with constitu-
asymptomatic elevations
tive tyrosine kinase activity
of lipase and amylase, to
is necessary and sufficient
a peak of 354 and 82 re-
for pathogenesis of chronic
spectively, which subsid-
phase CML. 1 Introduction of
ed despite continuation
imatinib, a tyrosine kinase
of therapy without dose
inhibitor, revolutionized ther-
modification. Within two
Figure
1:
Black
arrow
indicates
peripancreatic
stranding
consistent
with
pancreatitis.
apy of CML. Compared with
years of starting nilotinib,
interferon and Ara C, Imatinib
the patient achieved complete
resulted in improved major cy-
molecular remission of her
togenetic response, complete
CML. She continued nilotinib
maintenance therapy for the next two years with scan showed stranding of the pancreatic head, cytogenetic response and improved progression-
regular surveillance showing continued response suggestive of pancreatitis, no changes were not- free survival. Improvement in overall survival was
ed in the common bile duct, and gallbladder was not significant because of crossover. However,
(MR 4.5).
After four years of nilotinib therapy, the patient absent (Figure 1). MRCP performed did not reveal imatinib improved overall survival compared to
1,2
presented to the emergency department with a abnormalities in biliary drainage including intra- historic trials with interferon. With significant
seven-day history of abdominal pain in her right hepatic, extra hepatic, and common bile duct. The improvement, response is determined by mo-
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