CHECKPOINT INHIBITOR
IMMUNOTHERAPY; NOT SO NEW
KID ON THE BLOCK
Arash Rezazedeh Kalebasty, MD
I
mmunotherapy for treating cancer is not
a new concept. In 1891, William B. Coley performed intralesional injections of
streptococcal organisms in sarcoma patients
with a goal of enhancing immune response
and inducing tumor shrinkage. Intravesical
Bacillus Calmette-Guerin (BCG) has been
used to reduce the rate of superficial bladder cancer recurrence for many years. Other
examples include interferon alpha (IFN-alpha) and Interleukin-2
(IL-2) in treatment of kidney cancer and melanoma. High-dose
IL-2 is one of the most toxic therapies for cancer and due to these
potential acute toxicities, hospitalization and administration in an
ICU setting are standard.
Sipuleucel-T, an autologous cellular vaccine, became the first FDA
approved immunotherapy for treatment of metastatic prostate cancer
in 2010. Sipuleucel-T is generally well tolerated, with few serious
side effects, the most common being infusion-related. Although
treatment has demonstrated a survival advantage, response by way
of decreasing PSA or tumor shrinkage is generally not evident.
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LOUISVILLE MEDICINE
The oncology community has witnessed a rapidly evolving role
for immune checkpoint inhibitors in several types of cancer in recent years. This type of therapy unleashes the immune system and
prevents cancer cells from escaping the body’s immune surveillance.
Survival advantage has been shown in several types of cancer. Response to these agents has demonstrated prolonged disease stability, tumor shrinkage, and even complete responses in some cases,
indicating their potency and efficacy. In comparison to traditional
chemotherapy, these agents are generally better tolerated in the
majority of cancer patients. However, immunotherapy clinical trials
have excluded patients with any significant history of autoimmune
disorders due to fear of worsening these underlying diseases.
I wish to highlight immune related adverse events (irAEs) with
checkpoint inhibitor immunotherapy, and what we have learned to
date in managing these adverse effects.
Although irAEs can be transient in some cases, they can also be
severe and even fatal, if not identified quickly and managed properly.
As the name indicates, irAEs are mainly a result of the unleashed
immune system and are an “autoimmune problem.” Awareness of