ASH Clinical News March 2016 | Page 38

A Mile in Their Shoes

helping people. Rather than becoming a basic researcher,
the intersection between my love of biology and treating
patients seemed to be a career as a physician, especially as
a physician-scientist.
The weird thing about my story is that I would have
been an oncologist even if I had not had this personal
battle with leukemia. Starting in my undergraduate years,
I was really fascinated by the molecular biology of cancer.
At that time, oncology was one of the clearer examples
of how specific alterations could drive a disease and how
targeted therapies could try to eradicate that disease.
I was drawn to that idea. During
my second year of medical school,
I took a hematology course with a
great mentor, Scot Hickman, MD,
and, during my fourth year, I worked
with him at the oncology clinic at the
veterans’ hospital here in St. Louis.
Those experiences cemented my
interest in going into oncology as a
career.
A few months after that rotation, I
was diagnosed with leukemia.
How were you diagnosed with
leukemia?
At the end of my fourth year at Washington University, I felt fine and was
looking at residency programs and
interviewing for different residency
spots all over the country. I started
noticing, though, that I was feeling more fatigued than normal. I
attributed it to having been very busy
for the last few months and thought
I had viral infection like mononucleosis. I rested, but instead of things
getting better, things continued to
progress. I started developing night
sweats and was having bone pain and
progressive fatigue. Up until this time
I was perfectly healthy.
I had an opportunity to take a
few weeks off and went back to stay
with my parents outside of Chicago. I
thought if I could just rest and recuperate I could get over whatever viral
illness I had. I went home and things
continued to get worse. My fevers
started spiking one day so I went to an
urgent care center and convinced them
to draw bloodwork, which showed
that I was pancytopenic and had some
immature white blood cells circulating.
They weren’t leukemic cells, but the abnormality was due to the disruption of
my bone marrow. I immediately knew
that this was bad news, and it meant
that I likely had leukemia.
I came back down to St. Louis on
a Sunday, had a bone barrow biopsy
on Monday, and found out I had
leukemia on Tuesday. It was later
confirmed to be ALL. I dropped out
of the residency match and instead
was admitted to the hospital to start
induction chemotherapy.
After being diagnosed with ALL
did you question your decision to
pursue a career in medicine?

Never. I think that many colleagues, including some of
my professors in medical school, were concerned that
maybe oncology wasn’t the best choice for me, given my
own diagnosis. They thought I would be better served by
going into a field with more distance between my own
disease and my practice, but I never really questioned it
or had any serious doubts about still pursuing medicine.
More than anything, the diagnosis reinforced my commitment to studying leukemia and trying to come up
with better therapies to treat the disease.

When did you return to medical school?
I was on a leave of absence from medical school while
I was being treated – first with about nine months of
intensive chemotherapy, then with maintenance therapy.
When I started maintenance therapy, I joined a research
lab and did a year of research while completing my
chemotherapy. When that finished, I immediately finished my last month of medical school and enrolled into
residency.
I completed two years of residency and my first year
of clinical oncology fellowship at Washington University.

INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with
relapsed or refractory multiple myeloma who have received one to three lines of therapy.
IMPORTANT SAFETY INFORMATION
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. Some events occurred in patients with
normal baseline ventricular function. Death due to cardiac arrest has
occurred within one day of KYPROLIS administration.
• Monitor patients for clinical signs or symptoms of cardiac failure or
cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected.
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,
monitor all patients 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.
• Patients ≥ 75 years, the risk of cardiac failure is increased. Patients
with New York Heart Association Class III and IV heart failure,
recent myocardial infarction, conduction abnormalities, angina, or
arrhythmias may be at greater risk for cardiac complications and
should have a comprehensive medical assessment (including blood
pressure and fluid management) prior to starting treatment with
KYPROLIS and remain under close follow-up.
Acute Renal Failure: Cases of acute renal failure and renal insufficiency
adverse events (including renal failure) have occurred in patients
receiving KYPROLIS. Acute renal failure was reported more frequently in
patients with advanced relapsed and refractory multiple myeloma who
received KYPROLIS monotherapy. Monitor renal function with regular
measurement of the serum creatinine and/or estimated creatinine
clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome: Cases of Tumor Lysis Syndrome (TLS),
including fatal outcomes, have occurred in patients receiving KYPROLIS.
Patients with multiple myeloma and a high tumor burden should be
considered at greater risk for TLS. Adequate hydration is required prior
to each dose 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. Withhold KYPROLIS until
TLS is resolved.
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
patients receiving KYPROLIS. Some events have been fatal. In the event
of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension: Pulmonary arterial hypertension (PAH)
was reported in patients treated with KYPROLIS. 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.
Dyspnea: Dyspnea was reported in patients treated with KYPROLIS.
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.
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.

Venous Thrombosis: Venous thromboembolic events (including deep
venous thrombosis and pulmonary embolism) have been observed with
KYPROLIS. Thromboprophylaxis is recommended for patients being
treated with the combination of KYPROLIS with dexamethasone or with
lenalidomide plus dexamethasone. The thromboprophylaxis regimen
should be based on an assessment of the patient’s underlying risks.
• Patients using oral contraceptives or a hormonal method of contraception
associated with a risk of thrombosis should consider an alternative
method of effective contraception during treatment with KYPROLIS in
combination with dexamethasone or lenalidomide plus dexamethasone.
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. Premedicate
with dexamethasone to reduce the incidence and severity of infusion
reactions. Inform patients of the risk and of symptoms of an infusion
reaction and to contact a physician immediately if they occur.
Thrombocytopenia: KYPROLIS causes thrombocytopenia with
recovery to baseline platelet count usually by the start of the next
cycle. Thrombocytopenia was reported in patients receiving KYPROLIS.
Monitor platelet counts frequently during treatment with KYPROLIS.
Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure: Cases of hepatic failure,
including fatal cases, have been reported during treatment with
KYPROLIS. KYPROLIS can cause increased serum transaminases.
Monitor liver enzymes regularly regardless of baseline values.
Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy: Cases of thrombotic microangiopathy,
including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
(TTP/HUS), including fatal outcome have occurred in patients receiving
KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue
KYPROLIS if diagnosis is suspected. 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.
Posterior Reversible Encephalopathy Syndrome (PRES): Cases of
PRES have occurred in patients receiving KYPROLIS. PRES was formerly
known as Reversible Posterior Leukoencephalopathy Syndrome.
Consider a neuro-radiological imaging (MRI) for onset of visual or
neurological symptoms. Discontinue KYPROLIS if PRES is suspected
and evaluate. The safety of reinitiating KYPROLIS therapy in patients
previously experiencing PRES is not known.
Embryo-fetal Toxicity: KYPROLIS can cause fetal harm when
administered to a pregnant woman based on its mechanism of action
and findings in animals.
• Females of reproductive potential should be advised to avoid becoming
pregnant while being treated with KYPROLIS. Males of reproductive
potential should be advised to avoid fathering a child while being
treated with KYPROLIS. 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.
ADVERSE REACTIONS
• The most common adverse reactions occurring in at least 20% of
patients treated with KYPROLIS in the combination therapy trials:
anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia,
pyrexia, insomnia, muscle spasm, cough, upper respiratory tract
infecti on, hypokalemia.
You are encouraged to report negative side effects of prescription
drugs to the FDA. Visit MedWatch or call 1-800-FDA-1088.

Please see Brief Summary of full Prescribing Information on adjacent pages.
©2016 Onyx Pharmaceuticals, Inc., an Amgen Inc. subsidiary, Thousand Oaks, CA USA-171-120752 February 2016 Printed in USA

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ASH Clinical News