Optimizing Benefit and Limiting Immune-Related Adverse
Effects Following Checkpoint Inhibitor Blockade
W. Kimryn Rathmell, MD, PhD
Director, Division of Hematology
and Oncology
Cornelius Abernathy Craig Chair,
Department of Medicine
Vanderbilt University Medical Center
Nashville, Tennessee
s the population of patients treated with immune
checkpoint blockade expands and with even more
agents likely to be approved there is a growing need
for guidelines on managing immune-related adverse effects.
New recommendations from several national societies could
not be more timely because these now commonplace therapies
do not exhibit the typical side effects of cytotoxic or targeted
agents. Clinicians find themselves facing daily challenges to
manage immune-related adverse effects with appropriate
strategies and to recognize subtle complications that could be
overlooked or underestimated. This report highlights valuable
resources and strategies to adopt the latest advisories on managing
adverse events arising from immune checkpoint blockade.
As the footprint of immune checkpoint inhibitors (ICI)
grows larger across the landscape of oncology, especially
in renal cell carcinoma (RCC), this revolutionary change
in therapy is undergoing even closer scrutiny in view of
the speed with which these drugs have been adopted in
clinical practice after approval by the FDA. The speed of
approval, as noted in a recently published study1, is one
of the most important aspects of the ICI story, an aspect
sometimes overlooked in view of the potential benefits
conferred by these agents.
A recently published study showed that the majority
of patients eligible for ICI received treatment within a few
months of FDA approval, indicating an extremely rapid
42 Kidney Cancer Journal
implementation timeline.1 One of the long-standing concerns
about the adoption of novel therapeutics is that
they enter the market based on data from a selective
group of patients established by particular clinical trial
inclusion and exclusion criteria. For clinicians in the
community this can pose a challenge treating the general
population with key issues regarding lack of knowledge
surrounding the full side effect profiles.2,3 The good news
for those who have or are considering adopting ICI is that
there is a rapidly growing wealth of information on the
adverse effects likely to be encountered as well as emerging
effective consensus guidelines from leading medical
oncology societies.
Another challenge from the findings is the need to
reevaluate new and changing distributions of immune related
adverse events (ir-AE), in particular with the use of
recently approved combinations of immunotherapies in
RCC treatment. Postow et al tackled ten essential questions
practitioners will encounter as they consider the use
of ICI in RCC.4 The questions range from the most basic
(Why do these ir-AE occur? Can we predict who will have
ir-AE?), to a more nuanced consideration involving issues
including whether it is safe to continue or restart ICI after
patients experience an ir-AE. As the experience with ICI
expands beyond the early studies establishing their clinical
benefit, there is a growing awareness of an expanding
range of issues. In view of all the new studies, we have
reached an inflection point in the use of ICI in terms of
managing the associated adverse effects so that we can
move on to optimizing the benefit/risk ratio. In RCC, support
for the use of ICI began several years ago with the
report of phase 2 results on the safety of nivolumab in
patients with metastatic RCC.5
The rationale for ICI begins with an understanding of
mechanisms involved in the pathogenesis of RCC, mech-
Keywords: immune checkpoint blockade, immune-related adverse
effects, checkpoint inhibitors, PD-1, CTLA-4, dermatologic,
pulmonary, endocrine, management, corticosteroids.
Corresponding Author: Kathryn Eby Beckermann, MD, PhD, Chief
Academic Fellow, Division of Hematology/ Oncology
Vanderbilt University, 1211 Medical Center Drive, Nashville, TN
37232 katy.beckermann@vumc.org
Kathryn Eby Beckermann, MD, PhD
Clinical Instructor
Division of Hematology and Oncology
Vanderbilt University Medical Center
Nashville, Tennessee
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