Dataset Information

Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.

ABSTRACT:

Introduction

Immune checkpoint inhibitors (ICI) are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity; little data are available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI.

Methods

We conducted a retrospective review of sequential cancer patients treated with ICI between 2011 and 2017 at our institution. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. We calculated the incidence of ≥ grade 3 irTCP and overall survival (OS). Patient factors associated with irTCP were assessed.

Results

We identified 1,038 patients that met eligibility criteria. Overall, 89 (8.6%) patients developed grade ≥ 3 thrombocytopenia; eighteen were attributed to ICI (1.73% overall). Patients who developed grade ≥ 3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (4.17 vs. 10.8 month; HR. 1.94, 95% CI 1.13, 3.33; log-rank p = 0.0164). Patients with grade ≥ 3 irTCP also had worse survival compared to those without thrombocytopenia (4.17 vs. 13.31 months; HR 2.22, 95% CI 1.36, 3.62; log-rank p = 0.001). The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy (p = 0.059) and was not associated with cancer type, smoking status, age, gender, race, or line of therapy.

Conclusions

Unlike other irAEs, we found that irTCP was associated with worse overall survival. The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy.

SUBMITTER: Haddad TC

PROVIDER: S-EPMC9015999 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.

Haddad Tyler C TC Zhao Songzhu S Li Mingjia M Patel Sandip H SH Johns Andrew A Grogan Madison M Lopez Gabriella G Miah Abdul A Wei Lai L Tinoco Gabriel G Riesenberg Brian B Li Zihai Z Meara Alexa A Bertino Erin M EM Kendra Kari K Otterson Gregory G Presley Carolyn J CJ Owen Dwight H DH

Cancer immunology, immunotherapy : CII 20211007 5

<h4>Introduction</h4>Immune checkpoint inhibitors (ICI) are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity; little data are available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI.<h4>Methods</h4>We conducted a retrospective review of sequential cancer patients treated with ICI between 2011 and 2017 at our institution. All patients who ...[more]

PMID: 34618180

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) have led to dramatic improvements in survival a subset of patients with non-small cell lung cancer (NSCLC); however, they have been shown to cause life-threatening toxicity such as immune checkpoint inhibitor-related pneumonitis (CIP). Our previous studies have shown that chronic obstructive pulmonary disease (COPD) and circulating cytokines are associated with clinical outcomes in NSCLC patients receiving ICIs. However, the relationship between these factors and the development of CIP is unclear. In this study, we retrospectively assessed NSCLC patients receiving ICIs to identify CIP risk factors.MethodsThis retrospective cohort study reviewed medical records of NSCLC patients receiving ICIs targeting programmed cell death 1 (PD-1) or its ligand PD-L1 between March 2017 and December 2020 at Zhongshan Hospital Fudan University. CIP was diagnosed by the treating investigator. Clinical characteristics and baseline plasma cytokines were collected. Logistic regression was used to compare clinical characteristics and circulating cytokine levels between patients with and without CIP to identify CIP risk factors.ResultsOf 164 NSCLC patients who received ICIs, CIP developed in 20 cases (12.2%). The presence of COPD [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.130 to 45.798; P=0.037] and PD-L1 expression of ≥50% (OR, 7.184; 95% CI: 1.154 to 44.721; P=0.035) were independently associated with a higher incidence of CIP, whereas a higher baseline level of interleukin-8 (IL-8) was associated with a lower incidence of CIP (OR, 0.758; 95% CI: 0.587 to 0.978; P=0.033). The independent risk factors from final multivariate analysis were incorporated into a nomogram to predict the incidence of CIP. The nomogram model receiver operating characteristic (ROC) curve had a good predictive accuracy of 0.883 (95% CI: 0.806 to 0.959).ConclusionsIncreased risk of CIP independently associated with history of COPD, tumor PD-L1 expression ≥50%, and low baseline IL-8 level. The nomogram may hold promise for CIP risk assessment in the administration of ICIs.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have become standard treatments for lung cancer patients. Immune checkpoint inhibitor-related pneumonitis (CIP) was the leading cause of death among ICIs-related adverse events (irAEs). Recurrent episodes of CIP without rechallenge of ICIs were reported in several cases and maybe a unique feature of CIP. Knowledge gaps remain regarding the rate and risk factors associated to CIP's recurrence.MethodsData from 1,102 lung cancer patients receiving ICIs treatment between January 2016 and January 2021 were retrospectively collected and analyzed. CIP was diagnosed according to typical clinical features and/or new typical imaging changes. Recurrence of CIP (CIP-R) was defined as recurrent CIP after initial CIP improved after proper treatment. Logistic regression was used to assess risk factors associated with CIP recurrence.ResultsEighty out of 1,102 (7.26%) patients were diagnosed with CIP. Twenty of those 78 (25.64%) patients suffered CIP-R, 2 patients died and were therefore excluded from the denominator. The median onset of initial pneumonitis for patients without and with recurrence was 3.49 months [interquartile range (IQR), 0.26-31.93 months] and 2.78 months (IQR, 1.22-20.93 months), respectively (P=0.48). The median interval duration between initial CIP and CIP-R was 1.54 months (IQR, 0.98-16.70 months). Recurrence of CIP was more common in males (P=0.03), squamous histology (P=0.016), and in patients who received chest radiotherapy (P=0.049). The duration of prednisolone equivalent dose ≥15 mg/day in CIP-R was significantly shorter, at 3.71 weeks (2.86-6.57 weeks) compared with 6.36 weeks in those without recurrence (IQR, 3.12-9.86 weeks) (P=0.001). Non-squamous histology [odds ratio (OR), 0.182; 95% confidence interval (CI): 0.038-0.860; P=0.031] and prolonged administration of prednisolone equivalent dose ≥15 mg/day for more than 4 weeks (OR, 0.082; 95% CI: 0.02-0.342; P=0.001) were independently associated with a decreased odds of CIP-R development.ConclusionsCIP-R in a real-world lung cancer cohort is not uncommon, both in patients with and without rechallenge of ICIs. A duration of prednisolone equivalent dose ≥15 mg/day of at least 4 weeks during the tapering process of corticosteroids were recommend in patients with CIP.

Dataset Information

Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.

Introduction

Methods

Results

Conclusions

Publications

Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.

Similar Datasets

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