Pulling Back the Curtain: Alexis Thompson, MD, MPH
I was working with other investigators
who were making seminal observations in
the laboratory about the pathophysiology
of sickle cell disease and looking at new
molecular tools to be able to characterize
new forms of beta thalassemia, which is
another inherited blood disorder caused
by mutations in the same gene as sickle
cell disease.
After fellowship I further honed
my skills in the laboratory, working
with Randolph Wall, PhD, at the
University of California in Los Angeles
(UCLA) and learned so much from
his graduate students and postdocs.
I appreciated the support I received
from Stephen Feig, MD, my division
chief, that allowed me to get a stronger
foothold in the lab. The culture of
scientific discovery at the UCLA
Jonsson Comprehensive Cancer
Center and in the clinical programs
were so nurturing.
“I’ve worked
with many
students in
my laboratory
or acted as
a mentor ... ,
largely because
I know I
benefited
from those
relationships
and guidance.”
Throughout your career, I’m
sure you’ve had opportunities to
mentor younger hematologists
in training. What advice do you
share with them as they start
their careers?
I strongly recommend that they
focus first on their craft, whether in
the lab or at the bedside, and taking
themselves, their careers, and their
skills seriously. When I entered
medicine, there were so many things
that I wanted to do to change the
world immediately; I advise younger
trainees to stay focused. Later in
their careers, they can expand, but
at least early on, becoming excellent
in one area will allow them to be
24
ASH Clinical News
more effective in the long run. I also
strongly encourage them to find mentors
as they begin to take on more and more
interests and projects. It’s the challenge of
harnessing their excitement and energy
at the beginning of their careers – it
certainly inspires me!
One of the opportunities that I was
able to take advantage of while I was a
junior faculty member was receiving
funding through the Robert Wood
Johnson Foundation’s Minority Medical
Faculty Development Program, which
gave me a four-year period of financial
support and protected research time.
Eventually, that program spawned the
ASH-Harold Amos Medical Faculty
Development Program (AMFDP), which
was renamed and expanded in honor of
Harold Amos, PhD, who was the first
African-American to chair a department
at Harvard Medical School.
Knowing that I benefited personally
early in my career from having a lab
mentor and other career mentors through
that program, I became a strong advocate
in support of initiatives like the ASH-
AMFDP and Minority Medical Student
Awards Program. I’ve worked with many
students in my laboratory or acted as
a mentor for their clinical research or
for career development, largely because
I know I benefited from having those
BESPONSA™ (inotuzumab ozogamicin) is indicated for the treatment of adults
with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
AIM FOR DEEP
REMISSION
Deep remission refers to MRD-negative
remission, defi ned in the INO-VATE
ALL study as leukemic cells comprising
<1 x 10 -4 of bone marrow nucleated
cells per fl ow cytometry. 1
The effi cacy of BESPONSA was established on the basis of CR (35.8% [39/109; 95% CI,
26.8-45.5] with BESPONSA vs 17.4% [19/109; 95% CI, 10.8-25.9] with SC), the duration of
CR (8.0 months [95% CI, 4.9-10.4] with BESPONSA vs 4.9 months [95% CI, 2.9-7.2] with SC),
and the proportion of MRD-negative CR (89.7% [35/39; 95% CI, 75.8-97.1] with BESPONSA
vs 31.6% [6/19; 95% CI, 12.6-56.6] with SC) in the fi rst 218 randomized patients. 1
IMPORTANT SAFETY INFORMATION
WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE
DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION
SYNDROME) and INCREASED RISK OF POST–HEMATOPOIETIC STEM
CELL TRANSPLANT (HSCT) NON-RELAPSE MORTALITY (NRM):
• Hepatotoxicity, including fatal and life-threatening VOD, occurred in
patients who received BESPONSA. The risk of VOD was greater in
patients who underwent HSCT after BESPONSA treatment. The use
of HSCT conditioning regimens containing 2 alkylating agents and
last total bilirubin ≥ upper limit of normal (ULN) before HSCT were
signifi cantly associated with an increased risk of VOD
• Other risk factors for VOD in patients treated with BESPONSA
included ongoing or prior liver disease, prior HSCT, increased
age, later salvage lines, and a greater number of BESPONSA
treatment cycles
• Elevation of liver tests may require dosing interruption, dose
reduction, or permanent discontinuation of BESPONSA.
Permanently discontinue treatment if VOD occurs. If severe
VOD occurs, treat according to standard medical practice
• There was a higher post-HSCT non-relapse mortality rate in patients
receiving BESPONSA, resulting in a higher Day 100 post-HSCT
mortality rate
Hepatotoxicity, Including Hepatic VOD: Hepatotoxicity, including fatal and
life-threatening VOD, occurred in 23/164 patients (14%) during or following
treatment with BESPONSA or following subsequent HSCT. VOD was reported
up to 56 days after the last dose during treatment or follow-up without an
intervening HSCT. The median time from HSCT to onset of VOD was 15 days.
Patients with prior VOD or serious ongoing liver disease are at an increased
risk of worsening liver disease, including development of VOD, following
treatment with BESPONSA. Monitor closely for signs and symptoms of VOD;
these may include elevations in total bilirubin, hepatomegaly (which may be
painful), rapid weight gain, and ascites. For patients proceeding to HSCT,
the recommended duration of treatment with BESPONSA is 2 cycles. A third
cycle may be considered for patients who do not achieve a CR or CRi and
MRD-negativity after 2 cycles. Monitor liver tests closely during the fi rst
month post HSCT, then less frequently thereafter, according to standard
medical practice.
Grade 3/4 increases in aspartate aminotransferase, alanine aminotransferase,
and total bilirubin occurred in 7/160 (4%), 7/161 (4%), and 8/161 (5%)
patients, respectively.
Increased Risk of Post-HSCT Non-Relapse Mortality (NRM): There was a
higher post-HSCT NRM rate in patients receiving BESPONSA, resulting in a
higher Day 100 post-HSCT mortality rate. The rate of post-HSCT NRM was
31/79 (39%) with BESPONSA and 8/35 (23%) with investigator’s choice of
chemotherapy. In the BESPONSA arm, the most common causes of post-
HSCT NRM included VOD and infections. Monitor closely for toxicities post
HSCT, including signs and symptoms of infection and VOD.
Myelosuppression: Myelosuppression, and severe, life-threatening, and
fatal complications of myelosuppression, including hemorrhagic events
and infections, have occurred with BESPONSA. Thrombocytopenia and
neutropenia were reported in 83/164 patients (51%) and 81/164 patients
(49%), respectively. Febrile neutropenia was reported in 43/164 patients (26%).
Monitor complete blood counts prior to each dose of BESPONSA and
monitor for signs and symptoms of infection, bleeding/hemorrhage, or
other effects of myelosuppression during treatment and provide appropriate
management. As appropriate, administer prophylactic anti-infectives during
and after treatment with BESPONSA. Dose interruption, dose reduction, or
permanent discontinuation may be required.