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CLINICAL NEWS
with that one push, rather than over two consecutive days –
where the maximum concentration doesn’t get as high – will
be more important in determining the drug’s effectiveness,” he
proposed. “At the same time, we thought it would be associ-
ated with more toxicity. What’s perplexing is that we saw the
increased efficacy, but not increased toxicity.”
In both the once- and twice-weekly treatment groups,
95 percent and 97 percent of patients, respectively, expe-
rienced any-grade adverse event (AE), and 68 percent and
72 percent experienced a grade ≥3 AE. Rates of carfilzomib
discontinuation due to AEs (13% and 12%) and treatment-
related deaths (9 and 8) also were similar.
The higher carfilzomib dose was not associated with
increased hematologic toxicity or higher rates of “adverse
events of interest,” the authors observed. This included grade
≥3 peripheral neuropathy (n=0 for once-weekly and n=1 for
twice-weekly), acute renal failure (4 and 6), cardiac failure (3
and 4), ischemic heart disease (1 for each), and pulmonary
hypertension (0 and 1).
Though Dr. Berenson called these results “great news for
patients,” the study is limited by the lack of data on overall
survival, which will require longer-term follow-up. He added
that these data will be submitted to the U.S. Food and Drug
Administration to support approval of once-weekly carfilzo-
mib dosing.
The authors report financial relationships with Amgen,
which also provided funding for this study and editorial sup-
port for the presentation.
REFERENCE
Mateos MV, Moreau P, Berenson JR, et al. Once-weekly vs twice-weekly carfilzomib (K) dosing plus
dexamethasone (d) in patients with relapsed and refractory multiple myeloma (RRMM): Results
of the randomized phase 3 study A.R.R.O.W. Abstract #8000. Presented at the 2018 ASCO Annual
Meeting, June 1, 2018; Chicago, IL.
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 month s (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