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. 2022 Jul 15:12:934093.
doi: 10.3389/fonc.2022.934093. eCollection 2022.

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Yixuan Yu  1   2 , Yang Zhou  1 , Xu Zhang  1   2 , Kexin Tan  1   2 , Jiabin Zheng  2 , Jia Li  1   2 , Huijuan Cui  2
Affiliations

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Yixuan Yu et al. Front Oncol. .

Abstract

Background: Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis.

Methods: PubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, de novo immune-related adverse events (irAEs), discontinuation rate due to flare/de novo irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity.

Results: Twelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I2 = 71.7%) and 44.9% (95% CI: 29.0%-60.7%, I2 = 71.8%) for de novo irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3-4 flares occurred in 10.8% (95% CI: 5.3%-16.3%) of patients, and about 16.6% (95% CI: 10.7%-22.5%) of patients experienced grade 3-4 de novo irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%-30.8%, I2 = 68.7%). The median times to develop flare and de novo irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common de novo irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%-64.3%, I2 = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%-73.8%, I2 = 0).

Conclusions: The flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of de novo irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022320646.

Keywords: autoimmune disease (AID); cytotoxic T lymphocyte-associated protein 4 (CTLA-4); immune checkpoint inhibitor (ICI); immune-related adverse event (irAE); programmed cell death 1 (PD-1); programmed cell death ligand 1 (PD-L1); psoriasis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Search and selection flow diagram.
Figure 2
Figure 2
The pooled incidence of flare in patients with cancer and preexisting psoriasis. (A) The incidence of flare for any grades. (B) The incidence of flare for grades 3–4.
Figure 3
Figure 3
Subgroup analysis of the pooled incidence of flare in patients with cancer and preexisting psoriasis based on the class of immune checkpoint inhibitors (ICIs).
Figure 4
Figure 4
The pooled incidence of de novo immune-related adverse event (irAE) in patients with cancer and preexisting psoriasis. (A) The incidence of flare for any grades. (B) The incidence of de novo irAE for grades 3–4.
Figure 5
Figure 5
Subgroup analysis of the pooled incidence of de novo immune-related adverse event (irAE) in patients with cancer and preexisting psoriasis based on the class of immune checkpoint inhibitors (ICIs).
Figure 6
Figure 6
The pooled incidence of immune checkpoint inhibitor (ICI) therapy discontinuation due to flare/de novo immune-related adverse event (irAE) in patients with cancer and preexisting psoriasis.
Figure 7
Figure 7
The pooled efficacy in immune checkpoint inhibitor (ICI)-treated patient with preexisting psoriasis. (A) Objective response rate (ORR). (B) Disease control rate (DCR).
Figure 8
Figure 8
The pooled efficacy in immune checkpoint inhibitor (ICI)-treated patients with preexisting psoriasis and melanoma. (A) Objective response rate (ORR). (B) Disease control rate (DCR).
Figure 9
Figure 9
Risk of bias summary.
Figure 10
Figure 10
Egger’s test for included studies. (A) Flare. (B) De novo immune-related adverse event (irAE). (C) Discontinuation.
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