ASH Clinical News ACN_6.3_FullIssue | Page 3
In the INO-VATE ALL study, more patients achieved CR/CRi with MRD-negativity and
proceeded to HSCT after CD22-directed treatment with BESPONSA 1,2
SC
BESPONSA
CR/CRi rate*
P<0.0001 †
MRD-negativity rate
among responding
patients*
Overall
HSCT rate
80.7% n=88/109
(95% CI, 72.1-87.7) 29.4% n=32/109
(95% CI, 21.0-38.8)
78.4% n=69/88
(95% CI, 68.4-86.5) 28.1% n=9/32
(95% CI, 13.7-46.7)
48.2% n=79/164
(95% CI, 40.3-56.1) 21.6%
n=35/162
(95% CI, 15.5-28.7)
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). ‡ 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, febrile neutropenia, hemorrhage, abdominal
pain, pyrexia, VOD, and fatigue 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. The primary endpoints of the study were CR/CRi and OS. The secondary
endpoints were MRD-negativity, HSCT rate, and DoR. Inference regarding statistical signifi cance of secondary endpoints should not be
made. 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;
DoR=duration of remission; FLAG=fl udarabine, Ara-C, and granulocyte colony-stimulating factor; HiDAC=high-dose cytarabine; HR=hazard ratio;
HSCT=hematopoietic stem cell transplant; IV=intravenous; 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. † 1-sided P value using chi-square test. ‡ 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-0351-02
© 2020 Pfi zer Inc.
All rights reserved.
January 2020