fter Sharon Long was diagnosed with
stage IV non-small cell lung cancer
(NSCLC) at age 53 on Valentine’s Day
2014, she started chemotherapy. She
left her job as a nurse in anticipation
of the side effects, but the drugs
quickly stopped working. Her
doctor suggested a clinical trial,
recalls Long, who lives in New
When Long joined a trial of the immunotherapy
drug nivolumab, later given the brand name Opdivo,
in October 2014, she had a lemon-sized tumor under
her arm. About half a year later, the tumor was
gone. “We got to watch the tumor shrink to where
there’s absolutely nothing there,” says Long. “At first
I couldn’t imagine watching something shrink like
that. It was the coolest thing.”
Aside from some “really minor” symptoms, includ-
ing watering eyes and a runny nose, joint pain and
some fatigue, Long felt good. She stayed on Opdivo,
and her other tumors also disappeared or shrank.
Then, in October 2017, her tailbone began to hurt,
followed by mucus and then blood appearing in her
stool. Eventually, she was diagnosed with colitis, an
inflammation of the lining of the colon. After three
years of minimal side effects while on the drug, her
immune system was attacking her gut.
Opdivo, the drug Long took, is called a checkpoint
inhibitor. The first checkpoint inhibitor to reach
the market, Yervoy (ipilimumab), was approved by
the U.S. Food and Drug Administration (FDA) in
2011, originally only to treat metastatic melanoma.
Six checkpoint inhibitors are now FDA-approved
to treat 10 types of cancer. One of these drugs,
Keytruda (pembrolizumab), is also approved to treat
patients with metastatic solid tumors of any type
that have genetic characteristics shown to respond
to a checkpoint inhibitor.
Checkpoint inhibitors do not come with the acute,
predictable side effects associated with chemo-
therapy, such as hair loss, profound weakness and
nausea. “I call Opdivo the nice drug and chemo the
mean drug,” says Stephanie Langell of Long Neck,
Delaware, who was diagnosed with stage IV NSCLC
in 2015 at age 42 and is currently taking Opdivo.
“Obviously, cancer patients always have that fear of
cancer coming back, but I think my even bigger fear
However, checkpoint inhibitors come with their
own diverse side effects, and researchers and health
care providers are still learning how to best monitor
for them and treat them. Immune-related side effects
in the skin and gut, often showing up as rashes and
diarrhea, are among the most common. Other fre-
quently affected areas are the musculoskeletal system,
the lungs and the endocrine system, which includes
the thyroid and pituitary glands. More rarely, patients
can have problems affecting the nervous system, heart,
eyes, blood or kidneys.
While some side effects, such as heart problems,
tend to come on within a month of the start of treatment, others can take months or years to emerge.
Many side effects are reversible after patients take
drugs, usually steroids, to dial down their immune
response. But some immune reactions can lead to
lasting damage to organs, or, rarely, death.
“People think everything about the immune
system is good, and it’s here to protect us,” says
Jedd Wolchok, a medical oncologist at Memorial
Sloan Kettering Cancer Center in New York City.
Wolchok was a key investigator for the trial that led
to the approval of Yervoy. “We’re trying to get the
immune system to operate at the boundaries of what
it’s capable of doing. There’s the potential that your
The reason checkpoint inhibitors help the immune
system kill cancer is also the reason they cause side
effects. Checkpoint inhibitors “disable the molecular
brakes that keep our immune cells under control,”
Studying Side Effects
To provide support and to uncover issues that are important to patients taking
immunotherapy drugs, the nonprofit organization Cancer Support Community recently
launched its Immunotherapy & Me trial, which aims to test a series of immunotherapy
support resources, including online courses and materials, a registry to share
experiences, an app to track symptoms, distress screening, and a helpline staffed by
nurses. The study will be offered at nine oncology practices around the U.S.
The Lung Cancer Registry, a project sponsored by a coalition of lung cancer
organizations, also recently launched a study to better understand checkpoint inhibitor
side effects. Patients can sign up to share their experiences in the registry, which
asks questions about side effects, whether patients have had to delay or discontinue
treatment, and quality of life.