ASH Clinical News ACN_5.3_web | Page 29
CLINICAL NEWS
n=3 [60%] in the placebo group).
During the treatment period, major
bleeding occurred in six of 288 patients in
the apixaban group (2.1%) and in three of
275 patients in the placebo group (1.1%;
HR=1.89; 95% CI 0.39-9.24; p value not
reported).
Sixty-two patients died during study
follow-up: 35 in the apixaban group
(12.2%) and 27 in the placebo group
(9.8%). Most deaths (n=54; 87%) were
related to cancer or cancer progression.
“Our trial showed no significant between-
group difference in overall survival,” the
authors reported, likely reflecting the
advanced stage of cancer in this patient
population. “Although prevention of VTE
would ideally reduce overall mortality, a
different trial design and a much larger
sample would be required to address this
question.”
The authors noted several limitations
of this analysis. “As with all trials of
thromboprophylaxis involving patients
with cancer, between-trial comparisons
can be biased owing to differences in tu-
mor types in patients enrolled in the trial,”
they cautioned, noting that the inclusion
of few patients with colorectal or prostate
cancer might limit the generalizability
of these results to certain cancer types.
In addition, “only 5.9 percent of patients
had renal dysfunction, … so our results
CMYK
MORE CONVENIENT: Once-weekly dosing means 50% fewer KYPROLIS ® infusions
Kd70
NEW dosing option: 70 mg/m 2 Kd once weekly
KYPROLIS ®
infusion time Priming dose
of KYPROLIS ® Target therapeutic
dose of KYPROLIS ®
30 minutes 20 mg/m 2 on Day 1
of Cycle 1 to
evaluate tolerability 70 mg/m 2 starting on
Day 8 of Cycle 1
Treatment schedule
Administer KYPROLIS ® (70 mg/m 2 )
on 1 day each week for 3 weeks followed
by a 13-day rest period as part of a 28-day
treatment cycle
Continue until disease progression or
unacceptable toxicity occurs
Refer to the dexamethasone Prescribing Information for other concomitant medications.
References: 1. Amgen Inc. “FDA approves KYPROLIS ® (carfi lzomib) once-weekly 70 mg/m 2 in combination with dexamethasone (Kd70) for patients with relapsed
or refractory multiple myeloma.” News release; October 1, 2018. 2. KYPROLIS ® (carfi lzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc.
subsidiary. 3. Moreau P, Mateos M-V, Berenson JR, et al. Once weekly versus twice weekly carfi lzomib dosing in patients with relapsed and refractory multiple
myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018;19:953-964.
IMPORTANT SAFETY INFORMATION FOR KYPROLIS (cont.)
• Patients using hormonal contraception associated with a risk of
thrombosis should consider an alternative method of effective
contraception during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES)
Infusion Reactions • Cases of PRES have occurred in patients receiving KYPROLIS. If PRES
is suspected, discontinue and evaluate with appropriate imaging. The
safety of reinitiating KYPROLIS is not known.
Hemorrhage • In a clinical trial of transplant-ineligible patients with newly diagnosed
multiple myeloma comparing KYPROLIS, melphalan, and prednisone
(KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher
incidence of serious and fatal adverse events was observed in patients in
the KMP arm. KMP is not indicated for transplant-ineligible patients with
newly diagnosed multiple myeloma.
• Infusion reactions, including life-threatening reactions, have occurred.
Symptoms include fever, chills, arthralgia, myalgia, facial fl ushing,
facial edema, vomiting, weakness, shortness of breath, hypotension,
syncope, chest tightness, or angina. These reactions can occur
immediately following or up to 24 hours after administration. Premedicate
with dexamethasone to reduce the incidence and severity of infusion
reactions. Inform patients of the risk and of symptoms and seek
immediate medical attention if they occur.
• Fatal or serious cases of hemorrhage have been reported. Hemorrhagic
events have included gastrointestinal, pulmonary, and intracranial
hemorrhage and epistaxis. Promptly evaluate signs and symptoms
of blood loss. Reduce or withhold dose as appropriate.
Increased Fatal and Serious Toxicities in Combination with
Melphalan and Prednisone in Newly Diagnosed Transplant-
ineligible Patients
Embryo-fetal Toxicity
Hepatic Toxicity and Hepatic Failure • KYPROLIS can cause fetal harm when administered to a pregnant woman.
• Females of reproductive potential should be advised to avoid becoming
pregnant while being treated with KYPROLIS and for 6 months following
the fi nal dose. Males of reproductive potential should be advised to avoid
fathering a child while being treated with KYPROLIS and for 3 months
following the fi nal dose. If this drug is used during pregnancy, or if
pregnancy occurs while taking this drug, the patient should be apprised
of the potential hazard to the fetus.
Thrombotic Microangiopathy ADVERSE REACTIONS
The most common adverse reactions in the combination therapy trials:
anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia,
insomnia, muscle spasm, cough, upper respiratory tract infection,
hypokalemia.
Thrombocytopenia
• KYPROLIS causes thrombocytopenia with recovery to baseline platelet
count usually by the start of the next cycle. Monitor platelet counts
frequently during treatment. Reduce or withhold dose as appropriate.
• Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS
can cause increased serum transaminases. Monitor liver enzymes
regularly regardless of baseline values. Reduce or withhold dose as
appropriate.
• Cases of thrombotic microangiopathy, including thrombotic
thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS),
including fatal outcome, have occurred. Monitor for signs and symptoms
of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/
HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating
KYPROLIS is not known.
Please see Brief Summary of full Prescribing Information on
adjacent pages.
© 2018 Amgen Inc. All rights reserved. 09/18 USA-171-80362 Printed in USA
REFERENCE
Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent ve-
nous thromboembolism in patients with cancer. N Engl J Med. 2018
December 4. [Epub ahead of print]
h s
BETTER CONVENIENCE
may be less applicable to [these patients],
who are known to have a higher risk of
bleeding than patients with normal renal
function.”
The authors report relationships with
the Bristol-Myers Squibb–Pfizer Alliance,
which supported the trial. ●