Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Clinical and Molecular Information Collection
2.3. Statistical Analysis
3. Results
3.1. Patients Characteristics
3.2. Clinical Features in irAEs and Non-irAE Population
3.3. Molecular Features in irAE and Non-irAE Population
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CI | Confidence interval |
CTLA-4 | Cytotoxic T-lymphocyte–associated antigen 4 |
DCR | Disease control rate |
EGD | Esophagogastroduodenoscopy |
FANCA | Fanconi anemia complementation group A |
FDA | Food and Drug Administration |
GAs | Genomic alterations |
HGF | Hepatocyte growth factor |
HR | Hazard ratio |
ICIs | Immune checkpoint inhibitors |
IHC | Immunohistochemistry |
IrAEs | Immune-related adverse events |
IRB | Institutional review board |
KMT2C | Lysine (K) methyltransferase 2C |
LRP1B | Low-density lipoprotein (LDL) receptor-related protein 1B |
LOS | Length of stay |
MLL3 | Mixed-lineage leukemia protein 3 |
NGS | Next-generation sequencing |
NSCC-NOS | Non-small cell carcinoma, not otherwise specified |
NSCLC | Non-small cell lung cancer |
OR | Odds ratio |
ORR | Overall response rate |
OS | Overall survival |
PD-1 | Program death -1 |
PD-L1 | Programmed death-ligand 1 |
PFS | Progression-free survival |
SCLC | Small cell lung cancer |
TMB | Tumor mutation burden |
VS | Versus |
References
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IrAEs | No (%) |
---|---|
Pneumonitis | 10 (11.1%) |
Adrenal insufficiency | 4 (4.4%) |
Hypothyroidism | 4 (4.4%) |
Colitis | 4 (4.4%) |
Liver injury | 3 (3.3%) |
Nephritis | 2 (2.2%) |
Heart failure | 1 (1.1%) |
Pancreatitis | 1 (1.1%) |
Diabetic ketone acidosis | 1 (1.1%) |
Arthralgia | 1 (1.1%) |
Rash | 2 (2.2%) |
Other/Infection | 2 (2.2%) |
Multiple irAEs | 7 (7.8%) |
Total patients with irAEs | 28 (31.1%) 1 |
Characteristics | n = 90 (%) | IrAEs n = 28 (%) | No irAEs n = 62 (%) | p Values 1 |
---|---|---|---|---|
Median age at ICI (range 36–88) | 68.5 | 70.5 | 67.5 | ns |
Gender | <0.05 | |||
Women | 41 (45.6%) | 8 (28.6%) | 33 (53.2%) | |
Men | 49 (54.4%) | 20 (71.4%) | 29 (46.8%) | |
Smoking status | <0.01 | |||
Current | 11 (12.2%) | 6 (21.4%) | 5 (8.1%) | |
Former | 50 (55.6%) | 19 (67.9%) | 31 (50.0%) | |
Never | 29 (32.2%) | 3 (10.7%) | 26 (41.9%) | |
Histology | <0.01 | |||
Lung adenocarcinoma | 63 (70%) | 16 (57.1%) | 47 (75.8%) | |
Lung squamous | 14 (15.6%) | 4 (14.3%) | 10 (16.1%) | |
SCLC | 5 (5.6%) | 5 (17.9%) | 0 | |
Others 2 | 8 (8.9%) | 3 (10.7%) | 5 (8.1%) | |
ICIs with other therapy | ns | |||
Yes | 12 (13.3%) | 2 (7.1%) | 10 (16.1%) | |
No | 78 (86.7%) | 26 (92.9%) | 52 (83.9%) | |
PD-L1 | ns | |||
Negative | 16 (17.8%) | 5 (17.9%) | 11 (17.7%) | |
1% to <50% | 8 (8.9%) | 1 (3.6%) | 7 (11.3%) | |
50% and above | 21 (23.3%) | 7 (25.0%) | 14 (22.6%) | |
Not tested | 45 (50.0%) | 15 (53.6%) | 30 (48.4%) | |
Median lines of therapy (range 1–7) | 2 | 2 | 2 | ns |
Brain metastasis | ns | |||
Yes | 35 (38.9%) | 10 (35.7%) | 25 (40.3%) | |
No | 55 (61.1%) | 18 (64.3%) | 37 (59.7%) | |
Median length of stay (range 1–37) | 7 | 7 | 6 | ns |
Invasive Procedures after ICIs | irAEs (n = 28) | No irAEs (n = 62) |
---|---|---|
Bronchoscopy/lung biopsy | 6 (21.4%) | 6 (9.7%) |
EGD/Colonoscopy | 5 (17.9%) | 6 (9.7%) |
Thoracentesis | 2 (7.1%) | 8 (12.9%) |
Liver biopsy | 1 (3.6%) | 3 (4.8%) |
Skin biopsy | 1 (3.6%) | 0 |
Kidney biopsy | 1 (3.6%) | 0 |
Brain surgery | 1 (3.6%) | 2 (3.2%) |
Spine surgery | 0 | 1 (1.6%) |
Pericardium biopsy | 0 | 1 (1.6%) |
Total | 17 (60.7%) | 25 (40.3%) 1 |
Genomics | All (%) | IrAEs (%) | No irAEs (%) | OR (95% CI) | p Values 1 |
---|---|---|---|---|---|
TP53 | ns | ||||
Positive | 40 | 10 (66.7%) | 30 (58.8%) | ||
Negative | 26 | 5 (33.3%) | 21 (41.2%) | ||
Not tested | 24 | 13 | 11 | ||
KRAS | ns | ||||
Positive | 23 | 8 (40%) | 15 (26.3%) | ||
Negative | 54 | 12 (60%) | 42 (73.7%) | ||
Not tested | 13 | 8 | 5 | ||
EGFR | ns | ||||
Positive | 16 | 2 (10%) | 14 (24.6%) | ||
Negative | 61 | 18 (90%) | 43 (75.4%) | ||
Not tested | 13 | 8 | 5 | ||
LRP1B | 13.5 (1.7–166.1) | <0.05 | |||
Positive | 12 | 5 (83.3%) | 7 (26.9%) | ||
Negative | 20 | 1 (16.7%) | 19 (73.1%) | ||
Not tested | 58 | 22 | 36 | ||
PIK3CA | ns | ||||
Positive | 9 | 3 (20%) | 6 (11.8%) | ||
Negative | 57 | 12 (80%) | 45 (88.2%) | ||
Not tested | 24 | 13 | 11 | ||
MLL3 | 8.4 (1.3–49.3) | <0.05 | |||
Positive | 9 | 4 (66.7%) | 5 (19.2%) | ||
Negative | 23 | 2 (33.3%) | 21 (80.8%) | ||
Not tested | 58 | 22 | 36 | ||
TMB | ns | ||||
TMB-Low | 5 | 1 (33.3%) | 4 (26.7%) | ||
TMB-Intermediate | 9 | 1 (33.3%) | 8 (53.3%) | ||
TMB-High | 4 | 1 (33.3%) | 3 (20%) | ||
Not tested | 72 | 25 | 47 |
Risk Factors | Odds Ratio (95% CI) | p Values 1 |
---|---|---|
Gender | ||
Female | References | |
Male | 1.47 (0.43–4.99) | 0.5358 |
Smoking | ||
Never | References | |
Current | 3.61 (0.43–30.11) | 0.2363 |
Former | 3.44 (0.76–15.45) | 0.1073 |
MLL3 | ||
Negative | References | |
Positive | 6.52 (0.70–60.62) | 0.0991 |
LRP1B | ||
Negative | References | |
Positive | 8.00 (0.65–98.01) | 0.1037 |
Risk Factors | HR (95%CI) | p Values 1 |
---|---|---|
Gender | ||
Female | Reference | |
Male | 1.11 (0.57–2.15) | ns |
IrAEs | ||
No | Reference | |
Yes | 1.21 (0.50–2.92) | ns |
Interrupt ICIs due to irAEs | ||
No | Reference | |
Yes | 0.05 (0.01–0.19) | <0.001 |
Lines of therapy | ||
≥3 lines | Reference | |
2nd line | 0.62 (0.25–1.49) | |
1st line | 0.21 (0.07–0.58) | <0.01 |
EGFR | ||
Negative | Reference | |
Positive | 1.45 (0.55–3.77) | ns |
FANCA | ||
Negative | Reference | |
Positive | 11.30 (3.36–38.01) | <0.001 |
MET | ||
Negative | Reference | |
Positive | 11.17 (2.92–42.81) | <0.001 |
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Zhao, D.; Li, H.; Mambetsariev, I.; Chen, C.; Pharaon, R.; Fricke, J.; Baroz, A.R.; Kulkarni, P.; Xing, Y.; Massarelli, E.; et al. Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors. Cancers 2021, 13, 2653. https://doi.org/10.3390/cancers13112653
Zhao D, Li H, Mambetsariev I, Chen C, Pharaon R, Fricke J, Baroz AR, Kulkarni P, Xing Y, Massarelli E, et al. Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors. Cancers. 2021; 13(11):2653. https://doi.org/10.3390/cancers13112653
Chicago/Turabian StyleZhao, Dan, Haiqing Li, Isa Mambetsariev, Chen Chen, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Prakash Kulkarni, Yan Xing, Erminia Massarelli, and et al. 2021. "Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors" Cancers 13, no. 11: 2653. https://doi.org/10.3390/cancers13112653