Literature Scan
Continued from page 27
Arsenic Trioxide Plus ATRA: A Better Option for Patients
With Acute Promyelocytic Leukemia?
The combination of all-trans retinoic acid
(ATRA) and arsenic trioxide (ATO) could
be a safer and more effective treatment
option than ATRA and chemotherapy for
patients with acute promyelocytic leukemia
(APL), leading to higher event-free survival
(EFS), according to research correspondence
from Francesco Lo-Coco, MD, from the
University Tor Vergata in Rome, Italy, and
colleagues that was published in The New
England Journal of Medicine.1
“Treatment outcomes in patients with
newly diagnosed APL have improved
dramatically in the two decades since the
advent of ATRA and ATO,” Dr. Lo-Coco
IDELVION® [Coagulation Factor IX (Recombinant), Albumin Fusion Protein]
Lyophilized Powder for Solution for Intravenous Injection
Initial U.S. Approval: 2016
-------------------------DOSAGE FORMSAND STRENGTHS---------------------IDELVION is available as a lyophilized powder in single-use vials containing
nominally 250, 500, 1000 or 2000 IU.
BRIEF SUMMARY OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use IDELVION
safely and effectively. See full prescribing information for IDELVION.
-----------------------------CONTRAINDICATIONS ------------------------------Do not use in patients who have had life-threatening hypersensitivity reactions
to IDELVION or its components, including hamster proteins.
----------------------------INDICATIONS AND USAGE--------------------------IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIXFP), a recombinant human blood coagulation factor, is indicated in children
and adults with hemophilia B (congenital Factor IX deficiency) for:
• On-demand control and prevention of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to prevent or reduce the frequency of bleeding
episodes
Limitations of Use:
IDELVION is not indicated for immune tolerance induction in patients with
Hemophilia B.
--------------------------WARNINGS AND PRECAUTIONS----------------------• Hypersensitivity reactions, including anaphylaxis, are possible. Should
symptoms occur, discontinue IDELVION and administer appropriate
treatment.
• Development of neutralizing antibodies (inhibitors) to IDELVION may
occur. If expected Factor IX plasma recovery in patient plasma is not
attained, or if bleeding is not controlled with an appropriate dose,
perform an assay that measures Factor IX inhibitor concentration.
• Thromboembolism (e.g., pulmonary embolism, venous thrombosis,
and arterial thrombosis) may occur when using Factor IX-containing
products.
• Nephrotic syndrome has been reported following immune tolerance
induction with Factor IX-containing products in hemophilia B patients
with Factor IX inhibitors and a history of allergic reactions to Factor IX.
• Factor IX activity assay results may vary with the type of activated partial
thromboplastin time reagent used.
------------------------DOSAGE AND ADMINISTRATION-----------------------For intravenous use after reconstitution only.
Each vial of IDELVION is labeled with the actual Factor IX potency in
international units (IU).
• One IU of IDELVION per kg body weight is expected to increase the
circulating activity of Factor IX as follows:
° Adolescents and adults: 1.3 IU/dL per IU/kg
° Pediatrics (<12 years): 1 IU/dL per IU/kg
• Administer intravenously. Do not exceed infusion rate of 10 mL per
minute.
Control and prevention of bleeding episodes and perioperative
management:
• Dosage and duration of treatment with IDELVION depends on the severity
of the Factor IX deficiency, the location and extent of bleeding, and the
patient’s clinical condition, age and recovery of Factor IX.
• Determine the initial dose using the following formula:
• Required Dose (IU) = Body Weight (kg) x Desired Factor IX rise (% of
normal or IU/dL) x (reciprocal of recovery (IU/kg per IU/dL))
• Adjust dose based on the patient’s clinical condition and response.
Routine prophylaxis:
• Patients ≥12 years of age: 25-40 IU/kg body weight every 7 days. (2.1)
Patients who are well-controlled on this regimen may be switched to a
14-day interval at 50-75 IU/kg body weight.
• Patients <12 years of age: 40-55 IU/kg body weight every 7 days.
----------------------------ADVERSE REACTIONS--------------------------------The most common adverse reaction (incidence ≥1%) reported in clinical trials
was headache.
To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring
Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800FDA-1088 or www.fda.gov/medwatch.
----------------------USE IN SPECIFIC POPULATIONS--------------------------• Pediatric: Higher dose per kilogram body weight or more frequent dosing
may be needed.
Based on March 2016 version.
and colleagues wrote. “However, long-term
results for this strategy are still awaited.”
“ATRA combined with chemotherapy results in cure rates above 80 percent; however,
it is associated with a risk of severe infections
and secondary leukemias,” the authors
explained. “ATO combined with ATRA
has proved at least equally effective and
has more manageable toxic effects.”
In the randomized APL0406 trial,
researchers compared the two approaches
(ATRA + chemotherapy vs. ATRA +
ATO) in patients with non–high-risk
APL, defined as having white-cell counts
≤10 × 109/L. Earlier results from the trial
showed that, after a median follow-up of
34 months, patients in the ATRA + ATO
group achieved a significantly higher
rate of EFS at two years than those in the
ATRA + chemotherapy group (97% vs.
86%; p=0.02).2
In this update, 156 patients were included in an intent-to-treat analysis and
followed for a median of 53 months.
At 50 months, the EFS rate was again
higher in the ATRA + ATO group than
in the ATRA + chemotherapy group: 96
percent (95% CI 92-100) versus 81 percent (95% CI 73-91; p=0.003). The overall
survival rate was also higher: 99 percent
(95% CI 96-100) versus 88 percent (95%
CI 81-96; p=0.006).
Post-remission events in the ATRA +
chemotherapy group included six relapses
and five deaths (one of which was due
to secondary leukemia). In the ATRA +
ATO group, there were two relapses and
one death in remission; no further events
had been recorded in this treatment group
since the earlier publication of results.
Because the APL0406 trial enrolled
patients with non–high-risk APL, these
results are not applicable to patients with
high-risk APL. “Given the low number
of patients with high-risk disease who
were enrolled in [a similar, multicenter,
randomized trial] from the UK National
Cancer Research Institute, we believe that
a randomized trial comparing ATRA +
arsenic trioxide with ATRA + chemotherapy in such patients is still needed,”
the authors concluded.
Inclusion criteria and the small
number of patients enrolled may affect
the generalizability of study results. The
study, which was conducted at centers in
Austria, Germany, and Italy, also did not
address the insurance obstacles to receiving outpatient therapy that APL patients
may face in other countries. ●
REFERENCES
1. Lo-Coco F, Di Donato L, Schlenk RF. Targeted therapy alone for acute
promyelocytic leukemia. N Engl J Med. 2016;374:1197-8.
2. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med.
2013;369:111-21.
June 2016