The Journal of the Arkansas Medical Society Med Journal Feb 2020_Final | Page 13

Table 1
Classification Detectable BCR-ABL1 transcript
disease
to ABL1 transcript
ratio
MR2
≤ 1%
≤ 1:100 Log reduction Optimal duration of therapy to
reach classification
2 6 months
MR3 ≤ .1% ≤ 1:1000 3 12 months
MR 4 ≤ .01% ≤ 1:10000 4 Anytime
MR 4.5 ≤ .0032% ≤ 1:32000 4.5 Anytime
lecular testing with standardized real quantitative
polymerase chain reaction (RQ-PCR); sensitivity
is high for low-level residual disease (10-4 to 10-
5). Molecular response is assessed in accordance
with international scale (IS) as ratio of BCR-ABL1
transcripts to ABL1 transcripts or other inter-
nationally recognized control transcripts and
reported as BCR-ABL1% on a log scale 3 (Table
1). Long-term follow-up has been published for
imatinib cohort (median – 10.9 years), which
confirms excellent outcome. Ten-year overall sur-
vival was 83.3%; more importantly, CML specif-
ic survival was better in patients attaining major
molecular response at 12 and 18 months (MR3).
Despite these impressive results, about one-third
of patients need improved outcomes. 18 percent
of patients did not achieve complete cytogenetic
response; Table
10 percent of patients who attain com-
plete cytogenetic response lose their response,
and 4 to 8% of patients are intolerant to imatinib
therapy. Niltoinib, when compared with imatinib,
resulted in earlier and higher rates of major mo-
lecular response and lower risk of progression to
accelerated phase or blast. Long-term follow-up
confirmed improved response (MR4.5) 54% and
52% in two nilotinib arms compared to 31% with
imatinib. Long-term toxicities were not signifi-
cantly different, making this a valuable option.5-7
Our patient achieved and maintained complete
molecular response (MR4.5).
Our patient tolerated nilotinib therapy without
significant toxicities. Asymptomatic and transient
elevations of pancreatic enzymes that were noted
resolved without dose reduction or discontinua-
tion of nilotinib. Asymptomatic elevations in pan-
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creatic enzymes have been observed in approxi-
mately one-third of patients, including grade 3-4
in 18% of patients, which is usually not associated
with acute pancreatitis. Median time from start of
nilotinib to elevation of pancreatic enzymes was
three months. Pancreatic enzyme elevation was
isolated or transient in most patients. Occasion-
al drug interruption was necessary. 8 The under-
lying reason is unclear; suggested mechanisms
include inhibition of non-receptor tyrosine kinase
C-abl, calcium release from intracellular stores,
and accumulation of fatty acids in the acinar cell. 9
Acute pancreatitis is much less common, around
1%, and occurs relatively early after start of ni-
lotinib. Acute pancreatitis has been observed
after initiation of other tyrosine kinase inhibitors
in therapy of CML and other malignancies. De-
layed occurrence of pancreatitis has not been
reported thus far. 8-11 Acute abdominal symptoms,
magnitude of pancreatic enzyme elevation, and
CT imaging was consistent with the diagnosis of
acute pancreatitis on Atlanta criteria and graded
as mild, based on revised Atlanta criteria. 12 The
patient was diagnosed with acute drug-induced
pancreatitis by exclusion of other causes. Drugs
account for 2% of cases, usually mild to moder-
ate, and resolve with the discontinuation of drugs.
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