Mobile Health Apps
He is currently working on, and seeking
funding for, an app to measure appropriate
levels of physical activity in cancer survivors.
His rationale is that “cancer patients feel
that they need a specialized app. They don’t
want to use something like My Fitness Pal [a
calorie-counting, activity-tracking app for the
general population] because they are afraid
they might hurt themselves.”
The Sticking Point
mere 36 applications account for nearly half of
all health-care mobile app downloads, out of
more than 165,000 available apps.10
Dr. Krebs cited another roadblock to
adoption: the burden of data entry on the
user. Most health apps need the user to input
data about their activities; for example, weight
management tools require people to enter the
foods they eat, what time of day they are eating,
portion size, daily weight, and so on. The JMIR
study found that about half of health-care app
While people may freely report that they
downloaded health apps, the number of
downloads doesn’t necessarily reflect evidence
of use. If mobile health apps are exploding,
then why aren’t they on the home screen of
everyone’s smartphones or tablets and why
aren’t they being actively used?
In a survey of available health-care
mobile apps, the IMS Institute for Healthcare
Informatics pinpointed one reason why: A
KYPROLIS® (carfilzomib) for injection, for intravenous use
Brief Summary of Prescribing Information.
Please see the KYPROLIS package insert for full prescribing information.
1. INDICATIONS AND USAGE
Kyprolis in combination with lenalidomide and dexamethasone is indicated for the
treatment of patients with relapsed multiple myeloma who have received one to
three prior lines of therapy.
5. WARNINGS AND PRECAUTIONS
5.1 Cardiac Toxicities
New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure,
pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial
ischemia, and myocardial infarction including fatalities have occurred following
administration of Kyprolis. In clinical studies with Kyprolis, these events typically occurred
early in the course of Kyprolis therapy (<5 cycles). Death due to cardiac arrest has
occurred within a day of Kyprolis administration.
Withhold Kyprolis for Grade 3 or 4 cardiac adverse events until recovery, and consider
whether to restart Kyprolis at 1 dose level reduction based on a benefit/risk assessment.
While adequate hydration is required prior to each dose in Cycle 1, all patients should
also be monitored for evidence of volume overload, especially patients at risk for cardiac
failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac
failure or who are at risk for cardiac failure.
In patients ≥75 years of age, the risk of cardiac failure is increased. Patients with New
York Heart Association Class III and IV hear t failure, recent myocardial infarction, and
conduction abnormalities uncontrolled by medications were not eligible for the clinical
trials. These patients may be at greater risk for cardiac complications.
5.2 Acute Renal Failure
Cases of acute renal failure have occurred in patients receiving Kyprolis. Renal
insufficiency adverse events (renal impairment, acute renal failure, renal failure) occurred
in approximately 8% patients in a randomized controlled trial. Acute renal failure was
reported more frequently in patients with advanced relapsed and refractory multiple
myeloma who received Kyprolis monotherapy. This risk was greater in patients with a
baseline reduced estimated creatinine clearance (calculated using Cockcroft and Gault
equation). Monitor renal function with regular measurement of the serum creatinine and/
or estimated creatinine clearance. Reduce or withhold Kyprolis dose as appropriate.
5.3 Tumor Lysis Syndrome (TLS)
Cases of TLS, including fatal outcomes, have been reported in patients who received
Kyprolis. Patients with multiple myeloma and a high tumor burden should be considered
to be at greater risk for TLS. Ensure patients are well hydrated before administration
of Kyprolis in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering
drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and
manage promptly including interruption of Kyprolis until TLS is resolved.
5.4 Pulmonary Toxicity
Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse
infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have
occurred in less than 1% of patients receiving Kyprolis. Some events have been fatal. In
the event of drug-induced pulmonary toxicity, discontinue Kyprolis.
5.5 Pulmonary Hypertension (PAH)
PAH was reported in approximately 1% of patients treated with Kyprolis and was Grade 3
or greater in less than 1% of patients. Evaluate with cardiac imaging and/or other
tests as indicated. Withhold Kyprolis for PAH until resolved or returned to baseline and
consider whether to restart Kyprolis based on a benefit/risk assessment.
5.6 Dyspnea
Dyspnea was reported in 28% of patients treated with Kyprolis and was Grade 3 or
greater in 4% of patients. Evaluate dyspnea to exclude cardiopulmonary conditions
including cardiac failure and pulmonary syndromes. Stop Kyprolis for Grade 3 or 4
dyspnea until resolved or returned to baseline. Consider whether to restart Kyprolis based
on a benefit/risk assessment.
5.7 Hypertension
Hypertension, including hypertensive crisis and hypertensive emergency, has been
observed with Kyprolis. Some of these events have been fatal. Monitor blood pressure
regularly in all patients. If hypertension cannot be adequately controlled, withhold Kyprolis
and evaluate. Consider whether to restart Kyprolis based on a benefit/risk assessment.
5.8 Venous Thrombosis
Venous thromboembolic events (including deep venous thrombosis and pulmonary
embolism) have been observed with Kyprolis. In the combination study, the incidence of
venous thromboembolic events in the first 12 cycles was 13% in the Kyprolis combination
arm versus 6% in the control arm. With Kyprolis monotherapy, the incidence of venous
thromboembolic events was 2%. Thromboprophylaxis is recommended and should be based
on an assessment of the patient’s underlying risks, treatment regimen, and clinical status.
5.9 Infusion Reactions
Infusion reactions, including life-threatening reactions, have occurred in patients
receiving Kyprolis. Symptoms include fever, chills, arthralgia, myalgia, facial flushing,
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 of Kyprolis. Administer dexamethasone prior to Kyprolis to reduce the
incidence and severity of infusion reactions. Inform patients of the risk and of symptoms
and to contact a physician immediately if symptoms of an infusion reaction occur.
5.10 Thrombocytopenia
Kyprolis causes thrombocytopenia with platelet nadirs observed between Day 8 and
Day 15 of each 28-day cycle with recovery to baseline platelet count usually by the start
of the next cycle. Thrombocytopenia was reported in approximately 40% of patients
in clinical trials with Kyprolis. Monitor platelet counts frequently during treatment with
Kyprolis. Reduce or withhold dose as appropriate.
5.11 Hepatic Toxicity and Hepatic Failure
Cases of hepatic failure, including fatal cases, have been reported (<1%) during treatment
with Kyprolis. Kyprolis can cause increased serum transaminases. Monitor liver enzymes
regularly. Reduce or withhold dose as appropriate.
5.12 Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS)
Cases of TTP/HUS including fatal outcome have been reported in patients who received
Kyprolis. Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop
Kyprolis and evaluate. If the diagnosis of TTP/HUS is excluded, Kyprolis may be restarted.
The safety of reinitiating Kyprolis therapy in patients previously experiencing TTP/HUS is
not known.
5.13 Posterior Reversible Encephalopathy Syndrome (PRES)
Cases of PRES have been reported in patients receiving Kyprolis. Posterior
reversible encephalopathy syndrome (PRES), formerly termed Reversible Posterior
Leukoencephalopathy Syndrome (RPLS), is a neurological disorder which can present
with seizure, headache, lethargy, confusion, blindness, altered consciousness, and other
visual and neurological disturbances, along with hypertension, and the diagnosis is
confirmed by neuro-radiological imaging (MRI). Discontinue Kyprolis if PRES is suspected
and evaluate. The safety of reinitiating Kyprolis therapy in patients previously experiencing
PRES is not known.
5.14 Embryo-fetal Toxicity
Kyprolis can cause fetal harm when administered to a pregnant woman based
on its mechanism of action and findings in animals. There are no adequate and
well-controlled studies in pregnant women using Kyprolis. Carfilzomib caused
embryo -fetal toxicity in pregnant rabbits at doses that were lower than in patients
receiving the recommended dose.
Females of reproductive potential should be advised to avoid becoming pregnant while
being treated with Kyprolis. If this drug is used during pregnancy, or if the patient
becomes pregnant while taking this drug, the patient should be apprised of the potential
hazard to the fetus.
6. ADVERSE REACTIONS
The following adverse reactions have been discussed above and can be found the
Warning and Precautions section of the prescribing information. They include Cardiac
Toxicities, Acute Renal Failure, TLS, Pulmonary Toxicity, Pulmonary Hypertension, Dyspnea,
Hypertension, Venous Thrombosis, Infusion Reactions, Thrombocytopenia, Hepatic
Toxicity and Hepatic Failure, TTP/HUS and PRES.
6.1 Clinical Trials Safety Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared with rates in the
clinical trials of another drug, and may not reflect the rates observed in medical practice.
The safety of Kyprolis in combination with lenalidomide and dexamethasone (KRd) was
evaluated in an open-label randomized study in patients with relapsed multiple myeloma.
The median number of cycles initiated was 22 cycles for the KRd arm and 14 cycles for
the Rd arm.
Deaths due to adverse events within 30 days of the last dose of any therapy in the KRd
arm vs. Rd arm was 27/392 (7%) patients vs. 27/389 (7%) patients in the Rd arm. The
most common cause of deaths occurring in patients (%) cardiac 10 (3%) vs. 7 (2%),
infection 9 (2%) vs. 10 (3%), renal 0 (0%) vs. 1 (<1%), and other adverse events 9 (2%)
vs. 10 (3%). Serious adverse events were reported in 60% vs. 54% of patients in the
KRd arm vs. Rd arm. The most common serious adverse events reported in the KRd arm
verses the Rd arm were pneumonia (14% vs. 11%), respiratory tract infection (4% vs.
1.5%), pyrexia (4% vs. 2%), and pulmonary embolism (3% vs. 2%). Discontinuation due
to any adverse event occurred in 26% in the KRd arm vs. 25% in the Rd arm. Adverse
events leading to discontinuation of Kyprolis occurred in 12% of patients and the most
common events included pneumonia (1%), myocardial infarction (0.8%), and upper
respiratory tract infection (0.8%).
Common Adverse Events (≥ 10% in the KRd Arm) Occurring in Cycles 1–12
(Combination Therapy)
System Organ Class
Preferred Term
KRd Arm
(N = 392)
Any Grade
Rd Arm
(N = 389)
≥ Grade 3
Any Grade
≥ Grade 3
Blood and Lymphatic System Disorders
Anemia
138 (35%)
53 (14%)
127 (33%)
47 (12%)
Neutropenia
124 (32%)
104 (27%)
115 (30%)
89 (23%)
Thrombocytopenia
100 (26%)
58 (15%)
75 (19%)
39 (10%)
12 (3%)
Gastrointestinal Disorders
Diarrhea
115 (29%)
7 (2%)
105 (27%)
Constipation
68 (17%)
0
53 (14%)
1 (0%)
Nausea
60 (15%)
1 (0%)
39 (10%)
3 (1%)