From www.bloodjournal.org by guest on July 8, 2017. For personal use only.

l l l CLINICAL TRIALS AND OBSERVATIONS chemotherapy-free approach. Second, higher-

risk APL patients should still receive ATRA
Comment on Abaza et al, page 1275 plus chemotherapy outside of clinical trials.
Interestingly, some of the higher-risk
From occasional date to civil union in APL
-----------------------------------------------------------------------------------------------------
patients in the study by Abaza et al received
a single dose of idarubicin instead of GO as
part of their induction therapy, translating
Uwe Platzbecker UNIVERSITY HOSPITAL CARL GUSTAV CARUS DRESDEN
into a similar 5-year survival rate. In fact, the
European randomized intergroup study
In this issue of Blood, Abaza et al1 summarize the excellent long-term outcome of
APOLLO (NCT02688140) is currently
187 patients with acute promyelocytic leukemia (APL) undergoing a (mostly)
investigating 2 doses of idarubicin only in
chemotherapy-free rst-line treatment. This report is a follow-up and extension
addition to the ATRA/ATO regimen in
of 2 initial reports by the MD Anderson group,2,3 who were among the rst to
comparison with the standard ATRA-
explore all-trans-retinoic acid (ATRA)/arsenic trioxide (ATO)based therapy as
chemotherapy approach. It is hoped this
a rst-line regimen for APL patients. In the 2006 report, ATO was started 10 days
concept will become a success story for our
later than ATRA due to concerns about potential cumulative toxicity, but was
patients as well.
later modied to a concomitant administration from day 1 onward. The most
Conict-of-interest disclosure: U.P. has re-
important prognostic factor in APL is the white blood cell count at diagnosis,
ceived honoraria from Teva for participation in
which allows distinguishing patients with higher-risk or lower-risk disease (. or
advisory boards or lectures at conferences. n
#10 G/L). In both APL risk groups, an ATRA plus anthracycline-based
(idarubicin or daunorubicin) induction strategy is followed by 3 cycles of
chemotherapy-based consolidation therapy. In the past decade, this risk-adapted REFERENCES
therapeutic approach has led to nearly equivalent outcomes with regard to relapse 1. Abaza Y, Kantarjian H, Garcia-Manero G, et al. Long-
term outcome of acute promyelocytic leukemia treated with
rates in both patient risk groups. Still, relapses occur in up to 20% of patients all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.
receiving standard ATRA plus chemotherapy-based therapy. Blood. 2017;129(10):1275-1283.
2. Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of

I n the current study, all patients with higher-
risk disease, but also those with lower-risk
APL developing leukocytosis (45%), received
either gemtuzumab ozogamicin (GO) or
idarubicin in addition to ATRA/ATO. This
strategy is likely to represent an overtreatment
in the setting of lower-risk patients because
leukocytosis can be adequately managed by
hydoxyurea only.4,5 Only 7 patients (4%)
relapsed (5 of whom were higher risk). Relapses
occurred mostly within the rst year after
although disease recurrence remains a very rare
event with this regimen,4 patients should be
followed by MRD surveillance for a period of at
least 2 years.
Importantly, the data generated in this
study have provided the basis for several
subsequent randomized trials,4-6 which have
demonstrated the superiority of an ATRA/
ATObased regimen compared with the
ATRA-chemotherapy approach. Together
these studies paved the way for the recent
all-trans retinoic acid plus arsenic trioxide as an alternative
to chemotherapy in untreated acute promyelocytic
leukemia. Blood. 2006;107(9):3469-3473.
3. Ravandi F, Estey E, Jones D, et al. Effective treatment
of acute promyelocytic leukemia with all-trans-retinoic
acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin
Oncol. 2009;27(4):504-510.
4. Platzbecker U, Avvisati G, Cicconi L, et al.
Improved outcomes with retinoic acid and arsenic
trioxide compared with retinoic acid and
chemotherapy in nonhigh-risk acute promyelocytic
leukemia: nal results of the randomized Italian-
German APL0406 trial. J Clin Oncol. 2017;35(6):
605-612.

treatment, were captured at the minimal European Medicines Agency approval of ATO 5. Lo-Coco F, Avvisati G, Vignetti M, et al; Gruppo

residual disease (MRD) level, and could be
successfully salvaged in the majority of cases.
This observation highlights the fact that
ATRA and ATO in APL: from occasional date to civil
union. Professional illustration by Patrick Lane, ScEYEnce
Studios.
(in combination with ATRA) as rst-line
therapy of lower-risk APL.7 What a great
success story in hematology! ATRA and ATO
have now progressed beyond an occasional date
to a true civil union (see gure) for lower-risk
APL patients.
Which challenges now remain in APL
management? First, early death still occurs in
up to 20% of APL patients. Rapid diagnostics
and supportive care together with immediate
access to ATRA-based therapy, preferably in
specialized centers, are the goals of current
efforts in the APL eld. Even with the approval
of ATRA/ATO in lower-risk APL disease, we
continuously need real-life data from large
registries of APL patients treated with this
Italiano Malattie Ematologiche dellAdulto; German-
Austrian Acute Myeloid Leukemia Study Group; Study
Alliance Leukemia. Retinoic acid and arsenic trioxide for
acute promyelocytic leukemia. N Engl J Med. 2013;369(2):
111-121.
6. Burnett AK, Russell NH, Hills RK, et al; UK
National Cancer Research Institute Acute Myeloid
Leukaemia Working Group. Arsenic trioxide and all-
trans retinoic acid treatment for acute promyelocytic
leukaemia in all risk groups (AML17): results of
a randomised, controlled, phase 3 trial. Lancet Oncol.
2015;16(13):1295-1305.
7. European Medicines Agency. Trisenox. Available
at: http://www.ema.europa.eu/docs/en_GB/
document_library/Summary_of_opinion/human/
000388/WC500214157.pdf. Accessed 23 January 2017.
DOI 10.1182/blood-2017-01-759761
2017 by The American Society of Hematology

BLOOD, 9 MARCH 2017 x VOLUME 129, NUMBER 10 1235

 From www.bloodjournal.org by guest on July 8, 2017. For personal use only.

2017 129: 1235

doi:10.1182/blood-2017-01-759761

From occasional date to civil union in APL

Uwe Platzbecker

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