Cited by 331Cancer Immunotherapy and BiomarkersPharmacovigilance and Adverse Drug ReactionsImmunotherapy and Immune Responses

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Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade

Stroud, Chipman RG, Hegde, Aparna, Cherry, Cynthia, Naqash, Abdul R, Sharma, Nitika, Addepalli, Srikala, Cherukuri, Sulochana, Parent, Teresa, Hardin, Jessica, Walker, Paul·2019·Journal of Oncology Pharmacy Practice

DOI 10.1177/1078155217745144

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Abstract

BACKGROUND: Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs. METHODS: The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over one hour. C-reactive protein was drawn at first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital discharge within seven days. RESULTS: Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, serum sickness/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1-429). There was a statistically significant increase in C-reactive protein from a median of 23 mg/L (range 0.1-238.5) at baseline to 109.3 mg/L (21.5-350.4) at the time of index irAE, followed by a decrease to 19.2 mg/L (0.25-149) after tocilizumab ( p < 0.00001). Clinical improvement was noted in 27/34 patients (79.4%). Some patients (52.9%) required a single dose, while 38.2% required two, 8.8% required three and 1 patient required four doses. Twenty-seven doses were given in the inpatient setting (49.1%). Median time to discharge was four days (range 1-27). Seventy-four percent of patients were discharged home. For the 53 doses of tocilizumab that were delivered when infliximab was an option, there was a cost savings of $141,048.72 (WAC) during the 18 month study period. CONCLUSIONS: Tocilizumab may be a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.

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Authors: Stroud, C. R., Hegde, A., Cherry, C., Naqash, A. R., Sharma, N., Addepalli, S., Cherukuri, S., Parent, T., Hardin, J., & Walker, P.
Affiliations: East Carolina University (US)
Corresponding author: Hegde, Aparna
ORCID: Hegde, Aparna
Naqash, Abdul R
Walker, Paul
Venue: Journal of Oncology Pharmacy Practice
Publisher: SAGE Publications
Published: 2017-12-05
Volume: 25
Issue: 3
Pages: 551-557
ISSN: 1078-1552 (ISSN-L)
1477-092X
DOI: 10.1177/1078155217745144
OpenAlex: W2771433910
Cited by: 331
References: 26
Citations by year: 2026: 25 · 2025: 28 · 2024: 43 · 2023: 45 · 2022: 55 · 2021: 46 · 2020: 58 · 2019: 22 · 2018: 7 · 2017: 1
FWCI: 10.61
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Oncology Pharmacy Practice (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: tocilizumab, immune checkpoint inhibitors, immune-related adverse events, nivolumab, IL-6 receptor inhibitor, pneumonitis, serum sickness, C-reactive protein, lung cancer, hypophysitis, colitis, cerebritis, hypotension, hypoxemia
MeSH terms: Nivolumab, Adrenal Cortex Hormones, Adult, Aged, Aged, 80 and over, Female, Humans, Lung Neoplasms, Male, Middle Aged, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized

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Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade

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