Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis

Jennifer Strouse; Karmela Kimi Chan; Rachel Baccile; Gong He; Diana K. N. Louden; Mihai Giurcanu; Arohi Singh; John Rieth; Noha Abdel-Wahab; Tamiko R. Katsumoto; Namrata Singh; Sherin Rouhani; Pankti Reid

doi:10.3389/fimmu.2024.1499478

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Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis

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Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis

Jennifer Strouse, Karmela Kimi Chan, Rachel Baccile, Gong He, Diana K. N. Louden, Mihai Giurcanu, Arohi Singh, John Rieth, Noha Abdel-Wahab, Tamiko R. Katsumoto, …

Frontiers in immunology, Vol.15, 1499478

12/01/2024

DOI: 10.3389/fimmu.2024.1499478

PMCID: PMC11682972

PMID: 39737191

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Abstract

BackgroundThe impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.MethodsSearch was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science. We included case series, retrospective/prospective observational studies and interventional clinical trials. Individual-level data was analyzed using KM curves and Cox regression for overall survival (OS) and progression free survival (PFS). Time to SSIA was treated as a time-varying exposure using landmark analysis (landmark timepoint=3 months after irAE) to account for immortal time bias. For group-level data, meta-analysis compared the use of SSIA to No SSIA for irAEs.ResultsOf twenty-two publications with individual-level data, 147 patients with any cancer (57 CS, 90 CS-SSIA) and 65 with melanoma (18 CS, 47 CS-SSIA) underwent landmark analysis. Twenty-two publications underwent group-level evaluation and four were included in the meta-analysis. CS-SSIA versus CS showed higher risk of all-cause mortality and progression (HR 2.75, 95%CI: 1.44-5.27, p<0.01 and HR 1.75, 95%CI: 1.07-2.85, p=0.03, respectively). Melanoma showed worse OS and PFS for CS-SSIA versus CS (HR 5.68, 95%CI: 1.31-24.67, p=0.02 and HR 2.68, 95%CI: 1.12-6.40, p=0.03, respectively). In the meta-analysis of group-level data (n=2558), we found worse OS and PFS for CS-SSIA versus No SSIA (HR 1.58, 95%CI: 1.25; 2.01, p<0.01 and 1.70, 95%CI: 1.25-2.33, p<0.01). Tumor necrosis factor-alpha inhibitors (TNFi) were the most common SSIA. In the melanoma cohort, TNFi had worse OS and PFS versus CS (HR 6.46, 95%CI: 1.43-29.19, p = 0.02 and HR 7.49, 95%CI: 2.29-24.48, p<0.01, respectively). TNFi versus Other SSIAs showed a trend toward worse OS and worse PFS (HR 6.96, 95%CI: 0.90-53.65, p=0.06 and HR 21.5, 95%CI: 2.63-175.8, p<0.01, respectively). Meta-analysis showed a concern for TNFi compared to Other SSIA (HR 1.56, 95%CI: 1.17-2.09, p<0.01 respectively).ConclusionsWhile our results raise concern about the effects of CS-SSIA and TNFi for irAE therapy on tumor outcomes, prospective randomized controlled trials are needed to definitively assess the effect of SSIAs on tumor outcomes.

cancer immunotherapy

disease-modifying antirheumatic drugs (DMARDs)

ICI toxicity

immune related adverse events (irAEs)

steroid-sparing agents

tumor outcome

Details

Title: Subtitle: Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis
Creators: Jennifer Strouse - University of Iowa, Internal Medicine
Karmela Kimi Chan - Hospital for Special Surgery
Rachel Baccile - University of Chicago
Gong He - University of Michigan
Diana K. N. Louden - University of Washington
Mihai Giurcanu - University of Chicago
Arohi Singh - University of Chicago
John Rieth - University of Iowa
Noha Abdel-Wahab - Assiut University Hospitals
Tamiko R. Katsumoto - Stanford University
Namrata Singh - University of Washington
Sherin Rouhani - Massachusetts General Hospital
Pankti Reid - University of Chicago
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.15, 1499478
DOI: 10.3389/fimmu.2024.1499478
PMID: 39737191
PMCID: PMC11682972
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Publisher: Frontiers Media S.A
Grant note: National Institute for Health and Care Research10.13039/501100000272
The author(s) declarefinancial support was received for theresearch, authorship, and/or publication of this article. NS is supported by the National Institute of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes ofHealth under Award Number K23AR079588. NA-W is supportedby the National Institute of Allergy and Infectious Diseases of theNational Institutes of Health under Award Number K01AI163412and received the University of Texas MD Anderson Cancer CenterDoIM Development & Translational Science award, Bridge Fundingaward, Cancer Survivorship Seed Money Grant, InstitutionalResearch Grant, Prioritizing Research Innovation and MentoringExcellence (PRIME) award, Melanoma SPORE Career EnhancementProgram (CEP) award, and the Cyrus Scholar Award for OutstandingClinical Research. PR has received funding form COVID-19 Funds toRetain Clinical Scientists by the SECURED (Supporting Early CareerUniversity Researchers to Excel through Disruptions) SteeringCommittee as well as the University of Chicago Institute ofTranslational Medicine Clinical and Translational Science AwardK12/KL2 Grant 5KL2TR002387-05.
Language: English
Date published: 12/01/2024
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9984758293702771

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