Real-World Outcomes for Patients Treated With Immune Checkpoint Inhibitors in the Veterans Affairs System

La, Jennifer; Cheng, David; Brophy, Mary; Do, Nhan; Lee, Jerry S.H.; Tuck, David; Fillmore, Nathanael

doi:10.1200/cci.20.00084

Cited by 30 publications

(25 citation statements)

References 23 publications

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“…La and colleagues identified a median OS of NSCLC patients of 9.9 months in the second line ICI treatment, and a median OS of HNSCC patients of 7.4 months in real-world cohorts. 50 This is in line with our findings with a median OS of 8.7 months in a cohort consisting mainly of NSCLC and HNSCC. In the ST-ICI cohort, 32 patients had 0–1 previous treatments, while 57 patients had ≥2 of previous treatments.…”

Section: Discussionsupporting

confidence: 92%

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors

Zhou

Donaubauer²,

Frey³

et al. 2021

J Immunother Cancer

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BackgroundThe predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis.MethodsA total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients’ peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status.ResultsWhole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14high monocytes, CD8+/PD-1+ T cells, plasmacytoid dendritic cells, neutrophils, and CD3+/CD56+/CD16+ natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI.ConclusionOur study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood.Trial registration numberNCT03453892.

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Section: Discussionsupporting

confidence: 92%

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors

Zhou

Donaubauer²,

Frey³

et al. 2021

J Immunother Cancer

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“…Although some analyses have recently reported real-world outcomes of patients with advanced NSCLC treated with 1L I-O-based regimens in the United States, these studies have often had limited scope, including populations with targetable mutations [16], excluding patients with ECOG PS scores >1 [17], or focusing on patients treated in the Veterans Affairs system [18]. Additionally, some of the analyses only evaluated select I-O agents [17,[19][20][21] or had limited follow-up time [16].…”

Section: Introductionmentioning

confidence: 99%

Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer

et al. 2021

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Background: First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. Methods: Patients aged ≥18 years with confirmed advanced (stage III-IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. Results: Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3-11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3-12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8-12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4-15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. Conclusion: Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O-based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.

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“…This is likely due to patients with a lower comorbidity index being enrolled in these studies [ 69–71 ]. In a large Veterans Affairs study with 11 888 (non-ESKD) patients with different types of cancer receiving ICI, the overall survival ranged between 6.7 and 25.5 months [ 72 ]. This was largely dependent on the tumor type, with the longest survival seen in melanoma patients (25 months) and the shortest in patients with urothelial cancer receiving second-line ICI (6 months).…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review

Kitchlu

Jhaveri

Sprangers

et al. 2021

Clinical Kidney Journal

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Immune checkpoint inhibitors (ICI), immunomodulatory antibodies that are used to enhance the immune system, have substantially improved the prognosis of patients with advanced malignancy. As use of ICI therapy becomes increasingly widespread across different types of cancer, their use in patients receiving dialysis is likely to increase. In this review, we summarize the current literature on use of ICI in ESKD patients and provide aggregate data from reported cases and series. Based on available pharmacological information, ICIs require no dosing adjustment in ESKD patients. Analysis of the reported cases in the literature demonstrates similar incidence of immune-related adverse events in patients with ESKD receiving dialysis as compared to the general population (49%). Severe reactions graded as 3 and 4 have been seen in fifteen patients (16%). As such, it is important that these patients are monitored very closely for irAE, however the risk of these adverse events should not preclude patients on dialysis from receiving these therapies. Cancer remission (complete and partial) was seen in close to 30% of patients. Stable disease was seen in 28% and progression of disease in approximately 36% of patients. One-third of the patients died. Urothelial and renal cell cancer represented approximately half of all treated cancers, and accounted for approximately 50% of all deaths reported. Additional data in the dialysis population with use of ICI, and involvement in prospective studies, is needed to better assess outcomes, particularly within specific cancer types.

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Real-World Outcomes for Patients Treated With Immune Checkpoint Inhibitors in the Veterans Affairs System

Cited by 30 publications

References 23 publications

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors

Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer

Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review

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