CLINICAL NEWS
cycles of GO. Subsequent
maintenance therapy
consisted of ATRA plus
6-mercaptopurine plus
methotrexate for up to one
year.
Sixty-two patients (85%)
completed induction
therapy as planned, and 48
patients (66%) completed
all planned consolidation.
Thirty-two patients (44%)
completed maintenance
therapy. The “lower-thanexpected” rate of completion of all planned therapy
suggests that consolidation and/or maintenance
therapy may be “overly
toxic,” Dr. Lancet and colleagues explained.
Following treatment
initiation:
• 8 of the 73 patients (11%)
died within six weeks
• 3 patients (4%) voluntarily withdrew from the
study
Importantly, the early mortality rate was below the
investigators predefined
target rate (15%); the lower
early mortality rate also
supported rejection of the
null hypothesis, which
assumed a 30 percent early
death rate.
On the safety side, the
most common treatmentrelated grade 3 or 4 adverse events (AEs) during
induction included febrile neutropenia (33%),
aspartate aminotransferase/alanine aminotransferase elevation (12%), hypoxia/differentiation
syndrome (11%), hyperglycemia (11%), headache
(11%), and prolonged QTc (11%).
Among the 59 patients receiving consolidation,
the most common grade 3-4 AEs included febrile
neutropenia (52%), headache (14%), fatigue
(14%), and nausea (12%).
“The combination of ATO+ATRA+GO appears
safe and well-tolerated in patients with high-risk
APL,” Dr. Lancet and colleagues concluded, adding that the CCR analysis is ongoing. ●
Attendees mingle and discuss the content being presented during the ASCO meeting.
Treating the High-Risk APL
Patient: ATRA + ATO + GO
Might Be the Key
While the combinations of all-trans-retinoic
acid (ATRA) plus arsenic trioxide (ATO;
ATRA+ATO) and of ATRA+ATO plus gemtuzumab ozogamicin (GO; ATRA+ATO+GO) have
yielded good clinical outcomes for patients with
low-risk acute promyelocytic leukemia (APL),
patients with high-risk APL remain a therapeutic challenge and experience significant rates of
mortality and relapse. In a recent study presented
at the American Society of Clinical Oncology
meeting, Jeffrey E. Lancet, MD, and colleagues
found that induction therapy with the three-drug
ATRA+ATO+GO regimen was both feasible and
safe for these high-risk patients.
The phase II study was conducted by SWOG
investigators to validate the safety and efficacy of
this combination in high-risk APL. Primary objectives were assessment of early (6-week) death
rate and assessment of three-year continuous
complete remission (CCR).
Investigators enrolled 73 adults with newly
diagnosed, high-risk APL. Patients had a median
age of 46.5 years, and 52 percent were female.
Induction therapy consisted of 45 mg/m2 ATRA/
day on day 1 until CR, 0.15 mg/kg ATO/day on
day 10 until CR, and 9 mg/m2 GO on day 1.
Patients in CR received consolidation therapy
with two cycles of ATO, followed by ATRA plus
daunorubicin for two cycles, followed by two
ASHClinicalNews.org
REFERENCE
Lancet JE, Othus M, DeAngelo DJ, et al. Safety and tolerability of the combination of
ATRA + arsenic trioxide (ATO) + gemtuzumab ozogamicin (GO) in high-risk acute
promyelocytic leukemia (APL): Initial report of the SWOG/Alliance/ECOG S0535 trial.
Abstract #7016. Presented at the 2015 American Society of Clinical Oncology Annual
Meeting, Chicago, IL, May 31, 2015.
In an interview with ASH Clinical
News, Alan Burnett, MD, offers his
perspective on the ATRA combo in
APL patients. Watch the interview
by scanning the QR code.
Study Finds Clinical
Benefit for ERY001 in ALL
Asparaginase is a commonly prescribed treatment option for
acute lymphocytic leukemia (ALL), but its use can be limited
by its toxicities, including drug hypersensitivity. A recent
study found that the investigational drug ERY001 improved
pharmacokinetics, improved tolerability, and maintained
circulating aspariginase activity in relapsed ALL patients.
The results, presented by Yves Bertrand, MD, from the
Pediatric Hematology Department, IHOP and Claude
Bernard University, in Lyon, France, m ^H