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Featured research from recent issues of Blood
PAPER SPOTLIGHT
Examining Nilotinib to Prevent
Post-Transplant Relapse in
Patients With Ph+ Leukemia
In previous research published in
Blood, Paul A. Carpenter, MBBS,
from the Fred Hutchinson Cancer
Research Center in Seattle,
Washington, and co-authors
determined that using the
first-generation tyrosine kinase
inhibitor (TKI) imatinib early
after allogeneic hematopoietic
cell transplantation (alloHCT) is
feasible for relapse prevention
in patients with Philadelphia
chromosome–positive (Ph+,
BCR/ABL expressing) leukemia.
However, because alloHCT may
be performed in patients who are
resistant or intolerant to imatinib,
the authors questioned whether
using the second-generation TKI
nilotinib could improve outcomes
specifically for these patients.
In a Letter to the Editor
published in Blood, Dr. Carpenter
and colleagues presented updated
results from a single-arm study
of 57 patients enrolled between
September 2008 and September
2013. Patients were eligible for
inclusion if they were undergoing
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alloHCT, had BCR/ABL-expressing
acute lymphocytic leukemia (ALL)
or chronic myeloid leukemia (CML),
and were being treated with my-
eloablative conditioning. Patients
were excluded if they had a cardiac
condition or used a pacemaker.
During the study, 17 patients
became ineligible to begin relapse
prophylaxis, leaving 40 patients
in the final intent-to-treat (ITT)
population: 11 were imatinib-
resistant or -intolerant, and 29
were imatinib-sensitive. Thirty-
two patients had ALL (median age
= 42 years; range = 11-65 years)
and eight had CML (median age =
51 years; range = 18-54 years).
Following alloHCT, patients
who were intolerant or refractory
to imatinib began nilotinib 300 mg
(for adults) or 175 mg/m 2 (for
children) once- or twice-daily
prior to 80 days post-transplant
and were increased to a higher
dose on day 81. The study also
included patients with imatinib-
sensitive leukemia who began
imatinib 400 mg (for adults) or
260 mg/m 2 (for children) once-
daily, then, at 81 days post-
transplant, switched to nilotinib
400 mg (for adults) or 230 mg/m 2
(for children) once- or twice-daily
(depending on tolerability) for
one year.
After a median follow-up of 4.15
years (range not provided), 67.5
percent of the ITT population
were alive at three years, and
15 percent had relapsed. Nine
patients died during observation
(from relapse [n=4], non-relapse
mortality [n=3], and unknown
causes [n=2]), for a one-year
all-cause mortality rate of 22.5
percent.
Thirty-one patients (78%)
experienced 110 adverse events
(AEs), and 21 patients experienced
serious AEs. The most common
AEs were thrombocytopenia
(47.5%), lymphocytopenia (27.5%),
elevated aspartate and alanine
transaminase (25%), anemia
(17.5%), neutropenia (17.5%), and
cytomegalovirus viremia (17.5%).
The researchers noted that 43
AEs (39%) were either possibly,
proba