scholarly journals Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2653
Author(s):  
Dan Zhao ◽  
Haiqing Li ◽  
Isa Mambetsariev ◽  
Chen Chen ◽  
Rebecca Pharaon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Hospital Admissions ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Cox Models ◽  
Lung Cancer Patients ◽  
Thoracic Malignancies

Lung cancer patients undergoing systemic treatment with immune checkpoint inhibitors (ICIs) can lead to severe immune-related adverse events (irAEs) that may warrant immediate hospitalization. Patients with thoracic malignancies hospitalized at City of Hope while undergoing treatment with ICIs were identified. Pathology and available next-generation sequencing (NGS) data, including the programmed death-ligand 1 (PD-L1) status and clinical information, including hospitalizations, invasive procedures, and the occurrence of irAEs, were collected. Unpaired T-tests, Chi-square/Fisher’s exact test, and logistic regression were used to analyze our cohort. The overall survival (OS) was calculated and compared using univariate and multivariate COX models. Ninety patients with stage IV lung cancer were admitted after ICI treatment. Of those patients, 28 (31.1%) had documented irAEs. Genomic analyses showed an enrichment of LRP1B mutations (n = 5/6 vs. n = 7/26, 83.3% vs. 26.9%; odds ratio (OR) (95% confidence interval (CI): 13.5 (1.7–166.1); p < 0.05) and MLL3 mutations (n = 4/6, 66.7% vs. n = 5/26, 19.2%; OR (95% CI): 8.4 (1.3–49.3), p < 0.05) in patients with irAE occurrences. Patients with somatic genomic alterations (GAs) in MET (median OS of 2.7 vs. 7.2 months; HR (95% CI): 3.1 (0.57–17.1); p < 0.05) or FANCA (median OS of 3.0 vs. 12.4 months; HR (95% CI): 3.1 (0.70–13.8); p < 0.05) demonstrated a significantly shorter OS. Patients with irAEs showed a trend toward improved OS (median OS 16.4 vs. 6.8 months, p = 0.19) compared to hospitalized patients without documented irAEs. Lung cancer patients who required treatment discontinuance or interruption due to irAEs (n = 19) had significantly longer OS (median OS 18.5 vs. 6.2 months; HR (95% CI): 0.47 (0.28–0.79); p < 0.05). Our results showed a significant survival benefit in lung cancer patients hospitalized due to irAEs that necessitated a treatment interruption. Patients with positive somatic GAs in MET and FANCA were associated with significantly worse OS compared to patients with negative GAs.

Alterations in STK11 to limit response to immune checkpoint inhibitors in lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21503-e21503
Author(s):  
Jeremy Fricke ◽  
Isa Mambetsariev ◽  
Rebecca Pharaon ◽  
Angel Ray Baroz ◽  
Dan Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Rank Test ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Significant Difference

e21503 Background: The use of immune checkpoint inhibitors (ICIs) drastically transformed the treatment of lung cancer. However, a variety of response rates have been observed in patients due to intrinsic or acquired resistances. STK11 mutated patients represent a subgroup of lung cancer patients with diminished outcomes when given ICIs, with some of these patients developing hyperprogressive disease (HPD). Methods: In this study, a retrospective cohort of 384 lung cancer patients previously treated with ICIs was identified from the City of Hope Thoracic Registry (THOR) with a cutoff date of November 11, 2018. Next-generational sequencing (NGS) was performed on 246 patients. 24 of these patients were harboring an alteration in STK11. Data was collected on these patients until December 31, 2019. HPD was exclusively defined by time-to-treatment failure (TTF) < 2 months (TTF is defined as the time from the start of treatment with ICI to ICI discontinuation for any reason, including progression, patient preference, toxicity, or death). Overall survival (OS) and progression free survival (PFS) was started from the initiation of ICI therapy. OS and PFS was calculated between 2 groups (HPD vs non-HPD) using the Mantel-Cox Log-rank test. Results: Almost half (11/13; 45.8%) of the patients with STK11 developed HPD. There was a significant difference between HPD and non-HPD patients in median OS (2 vs 23 months; p = 0.0013) and median PFS (1 v 9 months; p < 0.0001). The median age was 66 (range, 41-90) years old with the majority of patients female (14/24; 58.3%). Most of the patients are deceased (16/24; 66.7%). 91.7% of STK11 patients histologically were adenocarcinoma and 91.7% were smokers with a median pack year history of 40 (range, 4-90). All of the patients had metastatic disease presenting with stage IV disease (21/24; 87.5%). ICI therapies used were pembrolizumab (11/24; 45.8%), Atezolizumab (8/24; 33.3%), nivolumab (4/24; 16.7%), and durvalumab (1/24; 4.2%). PD-L1 expression varied: negative (8/24; 33.3%), 1%- < 50% (7/24; 29.2%), ≥50% (4/24; 16.7%), and not reported (5/24; 20.8%). The most commonly occurring co-mutations were found in TP53 (14/24; 58.3%), KRAS (12/24; 50.0%), SMARCA4 (9/24; 37.5%), PRKDC (8/24; 33.3%) and LRP1B (8/24; 33.3%). Three patients had a pathological co-mutation that is targetable (1 ALK rearrangement, 1 EGFR exon 19 deletion, and 1 RET fusion). Conclusions: STK11 patients who developed HPD had worse OS and PFS compared to STK11 patients without HPD. These results are preliminary and additional analysis is needed to compare differences between various cohorts.

scholarly journals Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Cancer Patients ◽  
Predicting Factor ◽  
Type 3

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

Immune Checkpoint Inhibitors Rechallenge Efficacy in Non–Small-Cell Lung Cancer Patients

2020 ◽  
Vol 21 (5) ◽  
pp. e497-e510 ◽  
Author(s):  
Elisa Gobbini ◽  
Anne Claire Toffart ◽  
Maurice Pérol ◽  
Jean-Baptiste Assié ◽  
Michaël Duruisseaux ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients
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