leave modesty outside. Nobody is more interested in
your bathroom habits than I am.’”
Brahmer says that patients should be aware that
side effects can occur even when they are no longer
on a checkpoint inhibitor. The drugs themselves can
remain in the body for several months after treatment
ends, and the changes to the immune system can
persist even longer. “It’s always something a patient
has to keep in the back of their mind,” she says.
Some patients worry about telling their doctors
about side effects while taking immunotherapy drugs
because they fear they will be taken off a therapy that
is working. But Wolchok says that a patient whose
cancer is responding to a checkpoint inhibitor may
have already gotten the full benefit of the drug.
Further, taking steroids like prednisone—the most
common approach for treating checkpoint inhibitor
side effects—does not appear to make checkpoint
inhibitors significantly less effective, Wolchok
says. The steroids do tamp down certain damaging
immune responses, but they do not seem to impede
the immunotherapy drugs from working.
A final misconception is that if patients don’t have
side effects, it means their therapy isn’t working, says
Jeffrey Weber, a medical oncologist at the Laura and
Isaac Perlmutter Cancer Center at NYU Langone
Health in New York City. There may be some modest
associations between side effects and outcomes, he
adds, but it’s clear that patients with no side effects
can benefit from immunotherapy and that patients
with side effects do not always benefit.
The 1 Percent
Physicians tell patients who start on an immunotherapy to watch for specific symptoms that could be
indicative of dangerous adverse reactions. But they
also say that patients need to be aware of any changes
in their bodies and bring them up, because immunotherapies can affect almost any organ.
For instance, less than 1 percent of patients who
take checkpoint inhibitors called PD- 1 or PD-L1
inhibitors come down with a syndrome similar to
type 1 diabetes after their immune system attacks
insulin-producing cells in the pancreas.
Kevan Herold, an endocrinologist at Yale
University in New Haven, Connecticut, who coauthored the first case series on this diabetes-like
syndrome, says that some patients have ended up
in the intensive care unit before doctors realized
that their immune systems were attacking their
Checkpoint inhibitors are the most widely used type
of immunotherapy, but 2017 saw the approval of an
additional class of therapy: CAR-T cells.
Kymriah (tisagenlecleucel) was approved by the
U.S. Food and Drug Administration (FDA) in August
2017 for certain children and young adults with acute
lymphoblastic leukemia. Its approval was expanded
in May 2018 to include certain adult patients with
non-Hodgkin lymphoma. In October 2017, the FDA
approved Yescarta (axicabtagene ciloleucel) for
adults with certain types of non-Hodgkin lymphoma.
To make a CAR-T cell therapy, technicians remove
patients’ own T cells from their blood and then outfit
them with new receptors that cause them to target
specific types of cells. The two approved therapies
target immune cells called B cells in the patient’s body—
killing cancerous B cells along with healthy ones.
CAR-T cell therapies have led to lasting remissions
in some patients with advanced disease, but they can
be accompanied by unusual and severe side effects.
Most patients experience cytokine release syndrome
at varying levels of severity, says David Maloney, a
medical oncologist at the Fred Hutchinson Cancer
Research Center in Seattle who has led multiple CAR-T
cell therapy trials. Cytokine release syndrome occurs
when immune signals flood the body. It can lead to
low blood pressure, high fevers and general flu-like
symptoms. Many cytokine release syndrome symptoms
are treatable with a drug called Actemra (tocilizumab)
originally approved for rheumatoid arthritis.
Some patients develop neurotoxicity, which is likely
caused by disruption of the blood-brain barrier due to
high levels of cytokines. This disruption can allow fluid
to flow into the brain and, in some cases, lead to fatal
swelling. Neurotoxicity is treated with steroids and
has led to multiple deaths in clinical trials. “Hopefully
we’ll learn more about what causes [neurotoxicity] to
be so severe in some patients and be able to predict
and/or prevent it,” Maloney says.
As with any drug, deciding to have CAR-T cell therapy
is an individual choice that requires each patient to
analyze possible risks and benefits, says Maloney.
“You have to go into it with eyes wide open about the
fact this can have severe toxicities,” he says.
While CAR-T cell therapy side effects can be severe,
the therapy is used as a last option for patients. “The
patients currently being treated with CAR-T cells
have very few if any other options that would have any
chance of getting a major response,” Maloney says.
CAR-T Cell Therapy Side Effects