Pulling Back the Curtain: Clara Bloomfield, MD
happen early in a career.
That was followed by other research
that seemed to oppose the prevailing
wisdom at the time, like the discovery of
Philadelphia chromosome (Ph)–positive
acute lymphocytic leukemia (ALL) in
1978. At that time, everybody thought
Philadelphia chromosome only occurred
in chronic myeloid leukemia, but I
reported that approximately one-third of
patients with ALL had Ph-positive disease.
This had major consequences for how
those patients were treated.
Then, around 1982, I discovered
inv(16), an important chromosomal
abnormality in AML. Later, in 2004, we
found that patients with this abnormal-
ity had good outcomes with high-dose
cytarabine treatment, rather than stan-
dard chemotherapy treatment.
“[I advise
early-career
investigators
to] publish
what you find.
Don’t worry if
it contradicts
what others
have said,
as long as
your data are
sound.”
Now, my work focuses on molecular
findings with prognostic significance,
primarily in AML. This work has contrib-
uted significantly to the updated World
Health Organization Classification of
Hematologic Malignancies, as well as
the National Comprehensive Cancer
Network and the European LeukemiaNet
guidelines for the use of genetics in indi-
vidualized therapy in leukemias.
Much of my work was made pos-
sible through my role as chair of
the National Cancer Institute (NCI)
Cancer and Leukemia Group B Co-
operative Group’s Leukemia Correla-
tive Science Committee, which I held
for 17 years. During my tenure, we
updated clinical trials protocols to
include cytogenetics, molecular ge-
netics, leukemia tissue banking, and
other vital information for the future
of personalized medicine.
16
ASH Clinical News
On the flipside, were there any
major disappointments or setbacks?
Another simple answer: No.
I’ve been lucky through my career. I
became involved in a project early on that
turned out to be important. Who could
have known that, when I was told to study
older patients with AML, I would find what
I found? Right from the beginning, I was
working on a meaningful project, and one
that resulted in a promotion to full professor
in seven years. Not everybody is so lucky!
Of course, there is plenty of hard work
involved, as well, but that accelerated
timeline certainly gave me an advantage
throughout my career.
I could also attribute it to my personal-
ity: When an unanticipated problem comes
along, I’m quick to find a good solution. I
think that skill shields me from experienc-
ing any major disappointments, in a way.
Making a big to-do about a problem isn’t a
useful way to spend my time; I’d rather find
a solution and move on.
In that vein, is there any advice
that you would share with early-
career investigators?
Publish what you find. Don’t worry if it
contradicts what others have said, as long
as your data are sound. I’ve never believed
in ideas separated from data.
Also, get involved. For me, it was
FOR RELAPSED MULTIPLE MYELOMA
3 DOSING
OPTIONS
WITH
INDICATION Tumor Lysis Syndrome
IMPORTANT SAFETY INFORMATION
FOR KYPROLIS Pulmonary Toxicity
• KYPROLIS ® 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.
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 administration.
• Monitor patients for signs or symptoms of cardiac failure or 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 at 1 dose
level reduction based on a benefi t/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 fl uid intake as clinically appropriate.
• For 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 prior to starting treatment with KYPROLIS and remain under close
follow-up with fl uid management.
Acute Renal Failure
• Cases of acute renal failure, including some fatal renal failure events, and renal
insuffi ciency adverse events (including renal failure) have occurred. 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.
• Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred.
Patients with 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, and
withhold until resolved.
• Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and
acute diffuse infi ltrative pulmonary disease such as pneumonitis and interstitial
lung disease have occurred. Some events have been fatal. In the event of drug‐
induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension
• Pulmonary arterial hypertension (PAH) was reported. 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 based on a
benefi t/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 based on a benefi t/risk assessment.
Hypertension
• Hypertension, including hypertensive crisis and hypertensive emergency, has
been observed, some fatal. Control hypertension prior to starting KYPROLIS.
Monitor blood pressure regularly in all patients. If hypertension cannot be
adequately controlled, withhold KYPROLIS and evaluate. Consider whether to
restart based on a benefi t/risk assessment.
Venous Thrombosis
• Venous thromboembolic events (including deep venous thrombosis
and pulmonary embolism) have been observed. 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.