LETTERS
Minimizing waste during preparation
of blinatumomab infusions
A nnual cancer drug expenditures exceed $100 bil-
lion globally. 1 The Medicare Prescription Drug,
Improvement, and Modernization Act of 2003 prohibits
Medicare from negotiating drug prices.2 Since the pass-
ing of this legislation, the average price for a newly ap-
proved cancer drug has increased from $5,000–$10,000
per year of therapy to more than $100,000 in 2012.3,4
Despite the increased scrutiny of rising oncology drug
costs, on December 3, 2014, FDA approved one of the
most expensive oncology drugs the world has seen—
blinatumomab (Blincyto, Amgen, Thousand Oaks, CA).
Blinatumomab is a first-in-class, novel, CD19-
directed bispecific T-cell engager approved for the
treatment of patients with Philadelphia chromosome-
negative relapsed or refractory precursor B-cell acute
lymphoblastic leukemia (ALL). With an average whole-
sale price of $3,814.28 per vial and the requirement of
one vial daily for 28 days, blinatumomab can cost up
to $106,800 per treatment cycle.5 Patients may receive
up to five cycles of therapy; thus, the potential total
acquisition cost is $534,000. This does not include
markup costs or the costs of hospitalization, nursing,
and home care resources required to care for patients
receiving a 28-day course of continuous infusion. Fur-
thermore, with a maximum stability of 48 hours at room
temperature, bags must be changed every 24–48 hours,
further increasing the cost and complexity of therapy.6
The FDA-approved label recommends inpatient hos-
pital administration of the drug for a minimum of nine
doses on cycle 1 to monitor for the development of
severe cytokine release syndrome and neurologic toxic-
ity. Inpatient administration can be cost prohibitive for
many hospital systems, especially if drug acquisition
costs exceed diagnosis-related group reimbursement.
Despite its high cost, blinatumomab represents a true
breakthrough in the treatment of relapsed or refractory
B-cell acute lymphoblastic leukemia (ALL), with a 43%
The Letters column is a forum for rapid exchange of ideas among
readers of AJHP. Liberal criteria are applied in the review of submis-
sions to encourage contributions to this column.
The Letters column includes the following types of contributions:
(1) comments, addenda, and minor updates on previously published
work, (2) alerts on potential problems in practice, (3) observations or
comments on trends in drug use, (4) opinions on apparent trends or
controversies in drug therapy or clinical research, (5) opinions on public
health issues of interest to pharmacists in health systems, (6) comments
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cist. Reports of adverse drug reactions must present a reasonably clear
description of causality.
Short papers on practice innovations and other original work are in-
AM J HEALTH-SYST PHARM |
rate of complete response or complete response with
partial hematologic recovery, even in patients refrac-
tory to numerous lines of cytotoxic therapy.7 Eighty-
two percent of patients with one of these responses
achieved minimal-residual-disease negativity, which
is unprecedented among FDA-approved therapies for
relapsed or refractory ALL.
Despite the drug’s known efficacy, we have heard
anecdotal reports of institutions refusing provid-
ers the ability to prescribe blinatumomab due to
inpatient hospital costs. Some patient cases have
been taken to institutional ethics committees in or-
der to justify the refusal of therapy. Cost control has
been a major concern in these cases. At the Univer-
sity of Michigan Comprehensive Cancer Center, we
devised a method to cut blinatumomab inpatient
drug costs by more than 50% during the initial por-
tion of the first cycle; that cycle calls for blinatum-
omab 9 m g/day on days 1–7 and 28 m g/day on days 8
and 9. Instead of using nine vials ($34,328.52) over the
nine inpatient hospital doses required in cycle 1, we re-
constitute blinatumomab with four vials ($15,257.12)
(table).
One package of blinatumomab contains a 35-
m g vial of lyophilized blinatumomab and one
10-mL vial of i.v. solution stabilizer. The stabiliz-
er is required to prevent adsorption of blinatu-
momab to the infusing bag and tubing. Blinatum-
omab may be prepared as a 9-mg/24 hr infusion, 18-mg/48
hr infusion, 28-mg/24 hr infusion, or 56-mg/48 hr infu-
sion. To account for dead space in the infusion system,
the exact amounts of drug required for each of the
aforementioned infusions are 10.375, 21.25, 32.5, and
65 mg, respectively.
We administer the doses for days 1–6 from three
infusion bags prepared on day 1, with each bag contain-
ing blinatumomab 21.25 mg and stabilizer 5.5 mL and
cluded in the Notes section rather than in Letters.
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VOLUME 73 | NUMBER 2 | JANUARY 15, 2016  19
 LETTERS

Scheme for Preparing Nine-Day Course of Blinatumomab From Minimal Number of Blinatumomab Packages
Blinatumomab Stabilizer
Infusion Administration Source Source
Baga Days Contentsb (Amount)c (Amount)
A 1 and 2 Blinatumomab 21.25 mg + Package 1 (21.25 mg) Package 1 (5.5 mL)
stabilizer 5.5 mL
B 3 and 4 Blinatumomab 21.25 mg + Package 1 (13.75 mg) and Package 1 (4.5 mL)
stabilizer 5.5 mL package 2 (7.5 mg) and package 2 (1 mL)

C 5 and 6 Blinatumomab 21.25 mg + Package 2 (21.25 mg) Package 2 (5.5 mL)

stabilizer 5.5 mL
D 7 Blinatumomab 10.375 mg + Package 2 (6.25 mg) and Package 3 (5.5 mL)
stabilizer 5.5 mL package 3 (4.125 mg)
E 8 and 9 Blinatumomab 65 mg + Package 3 (30.875 mg) and Package 4 (5.6 mL)
stabilizer 5.6 mL package 4 (34.125 mg)
a
Bags A–C are prepared on day 1. Infusion from bag A begins on day 1; bags B and C are refrigerated until used on days 3 and 4 and on days
5 and 6, respectively. Preparation of Bag D begins on day 1 (with blinatumomab from package 2 and stabilizer from package 3) and refrigerated
until its infusion day (day 7), when its preparation is completed with the addition of blinatumomab from package 3. Bag E is prepared on day 7 and
refrigerated until use on days 8 and 9.
b
Bags A–C each deliver blinatumomab 9 mg/day, and each is infused continuously for 48 hours. Bag D delivers blinatumomab 9 mg and is infused
continuously for 24 hours. Bag E delivers blinatumomab 28 mg/day and is infused continuously for 48 hours. The excess blinatumomab in the bags
accounts for dead space in the infusion system.
c
Each package of blinatumomab contains blinatumomab 35 mg and stabilizer 10 mL.

infused continuously for 48 hours. Because reconsti- 2004. http://royce.house.gov/uploadedfiles/overview%20

tuted bags are stable for eight days when refrigerated of%20medicare.pdf (accessed 2015 Jun 11).
3. Light DW, Kantarjian H. Market spiral pricing of cancer drugs.
(while refrigerated reconstituted vials are stable for
Cancer. 2013; 119:3900-2.
only 24 hours), the bag for day 7 is partially prepared 4. Kantarjian H, Rajkumar S. Why are cancer drugs so expensive
on day 1 with 6.25 mg of blinatumomab from package in the United States, and what are the solutions? Mayo Clin
2 and 5.5 mL of stabilizer from package 3. This bag is Proc. 2015; 90:500-4.
refrigerated until its preparation is completed on day 5. Red Book Online [online database]. Greenwood Village, CO:
Truven Health Analytics (accessed 2015 Jun 11).
7 with the addition of 4.125 mg of blinatumomab from
6. Blincyto (blinatumomab) prescribing information. Thousand
package 3. The doses for days 8 and 9, also prepared on Oaks, CA: Amgen; 2014.
day 7, come from one bag containing blinatumomab 65 7. Topp MS, Gökbuget N, Stein AS et al. Safety and activity of
mg and stabilizer 5.6 mL and infused for 48 hours. Our blinatumomab for adult patients with relapsed or refractory
method calls for only four (rather than up to nine) vials B-precursor acute lymphoblastic leukaemia: a multicentre,
single-arm, phase 2 study. Lancet Oncol. 2015; 16:57-66.
of drug and stabilizer for the first nine days of therapy.
The blinatumomab package insert indicates that blina-
Bernard L. Marini, Pharm.D.
tumomab prepared in infusion bags has a maximum
Department of Pharmacy
storage time of eight days when refrigerated (2–8 °C).
Andrew R. Wechter, Pharm.D.
In our scheme, the maximum refrigerated storage time
Department of Pharmacy
for any bag is eight days.
We hope this compounding strategy will allow more Patrick W. Burke, M.D.
Division of Hematology and Oncology
patients to receive this unique and potentially lifesav- Department of Internal Medicine
ing therapy.
Dale Bixby, M.D.
1. IMS Institute for Healthcare Informatics. Developments in Division of Hematology and Oncology
cancer treatments, market dynamics, patient access and Department of Internal Medicine
value: global oncology trend report, 2015. www.imshealth.
com/portal/site/imshealth/menuitem.762a961826aad98f5 Anthony J. Perissinotti, Pharm.D.
3c753c71ad8c22a/?vgnextoid=cdec8a64ce90d410VgnVCM1 Department of Pharmacy
000000e2e2ca2RCRD&vgnextchannel=736de5fda6370410Vg ajperis@med.umich.edu
nVCM10000076192ca2RCRD&vgnextfmt=default (accessed University of Michigan Health System
2015 Jun 11). Ann Arbor, MI
2. O’Sullivan J, Chaikind H, Tilson S et al. CRS report for Con-
The authors have declared no potential conflicts of interest.
gress: overview of the Medicare Prescription Drug, Improve-
ment, and Modernization Act of 2003, updated December 6, DOI 10.2146/ajhp150420

20 AM J HEALTH-SYST PHARM | VOLUME 73 | NUMBER 2 | JANUARY 15, 2016

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