Muscle Visualization and Evaluation Methods for Immune Checkpoint Inhibitor-Related Myositis

Summary

Immune checkpoint inhibitors (ICIs) revolutionize cancer therapy but risk myositis; early multimodal evaluation (clinical, biomarkers, EMG, imaging, biopsy) optimizes diagnosis, management, and protocol standardization amid diagnostic challenges.

Abstract

Immune checkpoint inhibitors (ICIs) have fundamentally transformed the landscape of cancer therapy, yet their administration frequently correlates with immune-related adverse events (irAEs), amongst which myositis, an inflammatory disorder affecting the muscles, stands out. The prompt identification and thorough assessment of myositis associated with ICIs are imperative for effective therapeutic management and the enhancement of patient prognoses. In this report, we present a detailed evaluation of muscle function aimed at accurately diagnosing and appraising ICI-related myositis. Essential diagnostic methodologies, such as clinical evaluations, assessments of muscle strength, the analysis of laboratory biomarkers, electromyography (EMG), imaging modalities, and muscle biopsies, are scrutinized. The complexities involved in differentiating ICI-induced myositis from other autoimmune disorders, as well as non-autoimmune conditions, are thoroughly explored. A focused evaluation of muscle-specific factors is essential for refining diagnostic precision, optimizing patient management strategies, and establishing standardized protocols for assessment. By addressing these critical aspects, we can facilitate a more nuanced understanding of ICI-related myositis, ultimately leading to improved outcomes for patients affected by this condition. This comprehensive approach not only aids in the timely recognition of myositis but also contributes to the broader aim of maximizing the efficacy of immunotherapy in oncological settings.

Introduction

Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of various malignancies, offering a new dimension in cancer therapy by modulating the immune system to recognize and attack cancer cells¹. However, this novel class of drugs is not without its challenges, as it can lead to immune-related adverse events (irAEs) that may affect any organ system, including the musculoskeletal system².

Myositis, a condition characterized by inflammation and damage to muscle tissue, is one such irAE that usually manifests as muscle weakness, pain, and elevated muscle enzymes

Protocol

All patients provided written consent, and the study was approved by the Ethics Committee of Renji Hospital (ID: 2013-126), Shanghai, China.
NOTE: When ICI-myositis is suspected, a thorough diagnostic evaluation is essential. ICI-related myositis requires a comprehensive diagnostic approach that includes various evaluation methods to confirm the diagnosis, assess disease severity, and monitor treatment response. A detailed evaluation protocol is described here.

1. Medical history and symptom assessment

1. Obtain full medical history of patients with a history of cancer who have received immune checkpoint inhibitors (ICIs) tar....

Results

A flowchart is used to evaluate suspected ICI-myositis (Figure 1). The patient reported no pre-existing presentation or family history of IIM, nor known exposure to toxins. A review of medical history revealed that his symptoms presented 2 weeks after receiving the first round of anti-PD-1 immunotherapy for squamous cell carcinoma of the right upper lung.

Upon physical examination, the patient was conscious but unable to communicate due to generalized muscle weakn.......

Discussion

The landscape of cancer treatment has been revolutionized by the advent of immune checkpoint inhibitors, which have demonstrated unprecedented benefits in terms of durable responses across a spectrum of malignancies²⁵. However, the accompanying irAEs have emerged as a significant challenge due to their multi-systemic nature and unpredictable severity²⁶. Most studies to date have concentrated on well-known irAEs affecting endoc.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
ATPase Staining Kit (pH 10.6)	Solarbio	G2380	Reagent
ATPase Staining Kit (pH 4.6)	Solarbio	G2380	Reagent
C5b-9	Dako	M0777	Antibody
CD20	ZSGB-BIO	ZM-0039	Antibody
CD3	MXB	MAB-0740	Antibody
CD4	MXB	RMA-1086	Antibody
CD68	ZSGB-BIO	ZM-0060	Antibody
CD8	MXB	MAB-1031	Antibody
Cryostat	Leica Biosystems	CM1950	Instrument
Gum tragacanth powder	Ourchem	69013283	Chemical
Hematoxylin	BASO	BA4041	Chemical
Isopentane	Ourchem	XW7878406	Chemical
MHC-I	invitrogen	14-9983-82	Antibody
MHC-II	invitrogen	MA1-25914	Antibody
Modified Gomori Trichrome Stain	Solarbio	G3510	Reagent
MxA	Millipore	MABF938	Antibody
NADH-TR Staining Kit	Solarbio	N8120	Reagent
Oil Red O Staining Kit	Solarbio	G1261	Reagent
PAS Staining Kit	BASO	BA4080B	Reagent
SDH Staining Kit	Solarbio	G2000	Reagent