ASH Clinical News ACN_4.14_Full Issue_web | Page 27

UP FRONT
relationships and guidance. I’m
happy to pay it forward.
What aspects of medicine
have changed the most
since you started your
career?
The diagnosis and management
of hemoglobin disorders has
changed dramatically since the
start of my career. We have taken
the fundamental observations
about a disease’s pathophysiology
that were being made as I began
my career, converted those into
diagnostic testing that launched
newborn screening, and now,
fast-forward to a time when
those discoveries are being trans-
lated into therapies today. It has
been extraordinary.
Certainly, this includes gene
Dr. Thompson speaking at a meeting of the Sickle Cell Disease Coalition.
In the INO-VATE ALL study, more patients achieved MRD-negative complete
remission and proceeded to HSCT after CD22-directed treatment with BESPONSA 1,2
Median OS in patients treated with BESPONSA was 7.7 months (95% CI, 6.0-9.2) vs
6.2 months (95% CI, 4.7-8.3) in patients treated with SC (HR=0.75; P=0.0105). b The analysis
of OS did not meet a prespecifi ed boundary for statistical signifi cance of P=0.0104. 1,2
The most common (≥2%) serious adverse events were infection (23%), febrile neutropenia (11%),
hemorrhage (5%), abdominal pain (3%), pyrexia (3%), VOD (2%), and fatigue (2%) 1,2
Study design: INO-VATE ALL was a Phase 3, open-label, randomized (1:1) study of BESPONSA vs investigator’s choice of SC in 326 adult patients with relapsed
or refractory B-cell precursor ALL. SC included FLAG, HiDAC, or Ara-C + MXN. All patients were required to have ≥5% bone marrow blasts and to have
received 1 or 2 previous induction chemotherapy regimens for ALL. Patients with Ph+ B-cell precursor ALL were required to have failed treatment with ≥1 TKI
and SC. Single-agent BESPONSA was given by 1-hour IV infusion in 3 fractionated doses at 1.8 mg/m 2 each 3- to 4-week cycle, reduced to 3 fractionated doses
at 1.5 mg/m 2 per cycle after achieving CR/CRi, for up to 6 cycles. For patients proceeding to HSCT, the recommended treatment duration with BESPONSA is
2 cycles. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment. 1,3
Ara-C + MXN=cytarabine + mitoxantrone; CI=confi dence interval; CR=complete remission; CRi=CR with incomplete hematologic recovery; FLAG=fl udarabine, Ara-C,
and granulocyte colony-stimulating factor; HiDAC=high-dose cytarabine; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease;
OS=overall survival; Ph+=Philadelphia chromosome–positive; SC=standard chemotherapy; TKI=tyrosine kinase inhibitor; VOD=hepatic veno-occlusive disease.
Response assessments were performed in the fi rst 218 patients randomized, and survival analyses were completed in the full study population of 326 patients.
a
1-sided P value using chi-square test.
b
1-sided P value using log-rank test.
Learn more at BesponsaHCP.com
Infusion-Related Reactions: Infusion-related reactions (all Grade 2) were
reported in 4/164 patients (2%). Premedicate with a corticosteroid, antipyretic,
and antihistamine prior to dosing. Monitor patients closely during and for
at least 1 hour after the end of the infusion for the potential onset of
infusion-related reactions including symptoms such as fever, chills, rash,
or breathing problems. Interrupt the infusion and institute appropriate
medical management if an infusion-related reaction occurs. Depending
on the severity, consider discontinuation of the infusion or administration
of steroids and antihistamines. For severe or life-threatening infusion
reactions, permanently discontinue BESPONSA.
QT Interval Prolongation: Increases in QT interval corrected for heart rate
using Fridericia’s formula of ≥ 60 msec from baseline were measured in
4/162 patients (3%). Administer BESPONSA with caution in patients who
have a history of or predisposition to QTc prolongation, who are taking
medicinal products that are known to prolong QT interval, and in patients
with electrolyte disturbances. Obtain electrocardiograms and electrolytes
prior to treatment and after initiation of any drug known to prolong QTc,
and periodically monitor as clinically indicated during treatment.
Embryo-Fetal Toxicity: BESPONSA can cause embryo-fetal harm. Apprise
pregnant women of the potential risk to the fetus. Advise males and
females of reproductive potential to use effective contraception during
BESPONSA treatment and for at least 5 and 8 months after the last
dose, respectively. Advise women to contact their healthcare provider
if they become pregnant or if pregnancy is suspected during treatment
with BESPONSA.
Adverse Reactions: The most common ( ≥ 20%) adverse reactions observed
with BESPONSA were thrombocytopenia, neutropenia, infection, anemia,
leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia,
transaminases increased, abdominal pain, gamma-glutamyltransferase
increased, and hyperbilirubinemia. The most common ( ≥ 2%) serious adverse
reactions were infection, febrile neutropenia, hemorrhage, abdominal pain,
pyrexia, VOD, and fatigue.
Nursing Mothers: Advise women against breastfeeding while receiving
BESPONSA and for 2 months after the last dose.
INDICATION
BESPONSA is indicated for the treatment of adults with relapsed or
refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Please see brief summary of full Prescribing Information, including
BOXED WARNING, on adjacent pages.
References: 1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
2. Data on fi le. Pfi zer Inc, New York, NY. 3. Kantarjian HM, DeAngelo DJ, Stelljes M,
et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic
leukemia. N Engl J Med. 2016;375(8):740-753.
PP-INO-USA-0183-03
© 2018 Pfi zer Inc.
All rights reserved.
April 2018