Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors

Maillet, Denis; Corbaux, Pauline; Stelmes, Jean-Jacques; Dalle, Stéphane; Locatelli-Sanchez, Myriam; Perier‐Muzet, Marie; Duruisseaux, M.; Kiakouama-Maleka, Lize; Boespflug, Amélie; Péron, Julien

doi:10.1016/j.ejca.2020.03.017

Cited by 55 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, the correlation between any grade irAEs and survival outcome in different cancer types was also analyzed, but there was no correlation in common tumors such as melanoma and bladder cancer (which may be due to the small samples). Only in lung cancer patients with a large sample size, the occurrence of any grade irAEs was significantly associated with better mPFS (13.47 vs. 4.13 mo, HR � 2.66, p � 0.007) and mOS (not reached vs. 10.33 mo, HR � 3.65, p � 0.001), which is consistent with most other retrospective studies on NSCLC, including some that appropriately consider the time-varying nature of the occurrence of irAEs [11,40,41]. We considered that overall heterogeneity of the results was related to the types of ICIs, unique characteristics of patients, and the heterogeneity of tumor types.…”

Section: Discussionsupporting

confidence: 85%

“…A report of NSCLC showed that patients with "multi-site" irAEs survived longer than patients with "single-site" irAEs only [42]. However, Maillet et al [11] showed that OS was more associated with the occurrence of "single-site" irAEs (p < 0.0001). erefore, it is not clear whether the number of irAEs can differentially affect clinical outcomes in patients with tumors treated with ICIs.…”

Section: Discussionmentioning

confidence: 99%

“…e basis of irAEs is the activation of abnormal autoimmune T lymphocytes, indicating a possible association between their occurrence and clinical benefit. Although a number of recent studies have reported this view [11][12][13], data on the impact of irAEs on long-term survival outcomes in clinical practice are conflicting and have not been clarified. Based on this, this retrospective study aimed to comprehensively analyze the convenient and available indicators that can predict the efficacy of ICIs in patients with advanced pancancer who were treated with multiple types of ICIs in the real world and focused on the correlation between ICIsefficacy and irAEs that are currently of great concern to clinicians and clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Correlation of Peripheral Blood Parameters and Immune-Related Adverse Events with the Efficacy of Immune Checkpoint Inhibitors

Bai

Chen

et al. 2021

Journal of Oncology

View full text Add to dashboard Cite

Objective. We aimed to retrospectively analyze the predictors of immune checkpoint inhibitors (ICIs)-efficacy in patients with advanced pancancer who were treated with various ICIs in the real world and focused on the correlation between ICIs-efficacy and immune-related adverse events (irAEs). Methods. We retrospectively analyzed data from 103 patients with advanced pancancer treated receiving various ICIs in the First Hospital of Jilin University from January 1, 2016 to August 1, 2020. Survival probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier curves and log-rank tests and the multivariate Cox proportional hazards model. Receiver-operating characteristic curve was used to determine a cutoff value for parameters and area under the curve. Correlations between the two variables were analyzed by logistic regression. Results. All patients were analyzed for survival predictors of OS, while 87 of 103 patients experienced evaluable disease progression of immunotherapy and were included in the analysis of predictors of PFS. First, we found that lower platelet (cutoff = 201.5 × 109/L) and lactate dehydrogenase (LDH) (cutoff = 227 U/L) were independently associated with significantly improved PFS, while lower platelet-lymphocyte ratio (cutoff = 206.5), absolute monocyte count (cutoff = 0.62 × 109/L), and LDH (cutoff = 194.5 U/L) were significantly and independently associated with better OS. In the analysis of the immune cell subgroup, a lower absolute countof CD8+CD28−suppressor T cells was an independent factor associated with better PFS (6.60 vs.4.13 months (mo), hazard ratios (HR) = 3.17, p = 0.0038), and OS (29.4 vs. 9.57 mo, HR = 3.05, p = 0.03). Second, the results of the analysis for irAEs showed that patients with any grade irAEs had higher objective response rate (30% vs. 10%, HR = 4.34, p = 0.009), disease control rate (69.7% vs. 50%, HR = 2.3, p = 0.028), PFS (8.37 vs. 3.77 mo, HR = 2.02, p = 0.0038), and OS (24.77 vs.13.83 mo, HR = 1.84, p = 0.024). Moreover, the groups with irAEs of grade ≥2 and with “multi-site” irAEs had significantly better PFS and OS ( p < 0.05) compared with the other groups. We also proved that endocrine irAEs (usually thyroid dysfunction) were significantly associated with better mPFS ( p = 0.01), and hepatic irAEs were significantly associated with better mOS ( p = 0.023). Conclusions. This retrospective study explored the availability and effectiveness of some cost-effective and readily available blood biochemical parameters in routine clinical practice to predict the ICIs-efficacy and demonstrated the predictive role of different categories of irAEs on efficacy.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Correlation of Peripheral Blood Parameters and Immune-Related Adverse Events with the Efficacy of Immune Checkpoint Inhibitors

Bai

Chen

et al. 2021

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…These results are in conflict with an earlier analysis performed on the same cohort, also conducted by Hospices Civils de Lyon’s medical team [ 25 ]. This previous analysis, performed on a smaller cohort and with shorter follow-up, found a positive association between grade ≥2 irAEs and long-term outcomes with an HR for PFS of 0.63 (95% CI 0.50–0.81; p = 0.00022) and an HR for OS of 0.57, (95% CI 0.43–0.74; p < 0.0001).…”

Section: Discussioncontrasting

confidence: 98%

Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Bruyère

Souquet

Dalle

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

show abstract

“…Our patient showed a clinical response to nivolumab. An association between the efficacy of ICI treatment and the occurrence of irAEs has been reported in several cancers, especially melanoma and non-small cell lung cancer (NSCLC) [ [21] , [22] , [23] ]; however, such an association has not been observed in patients with MPM. Although any type of irAE was related to better outcomes of ICI treatment, analyses of the efficacy of ICIs in patients who develop hematological irAEs are limited.…”

Section: Discussionmentioning

confidence: 99%

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma

Sakakibara‐Konishi

Sato

et al. 2020

Respiratory Medicine Case Reports

View full text Add to dashboard Cite

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive tumor. Nivolumab showed durable antitumor effect in patients with recurrent MPM and was approved for those patients in Japan in 2018. Immune related adverse event (irAE) is occurred in various organs and is suggestive to be related to better outcome of nivolumab. Frequency of hematological irAE is low and there are few reports about hematological irAE and association between irAE and outcome of nivolumab in patients with MPM. We present a case of recurrent MPM who responded to nivolumab treatment and experienced nivolumab-induced immune thrombocytopenia (ITP). Although high dose dexamethasone was administered and platelet count increased transiently, re-administration of dexamethasone was required to maintain normal count of platelet. The careful and intensive management of ITP treatment is necessary in cases who show no response or relapse to initial glucocorticoids treatment. This is the first report about nivolumab-induced ITP and association with response to nivolumab in MPM.

show abstract

Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors

Cited by 55 publications

References 27 publications

Correlation of Peripheral Blood Parameters and Immune-Related Adverse Events with the Efficacy of Immune Checkpoint Inhibitors

Correlation of Peripheral Blood Parameters and Immune-Related Adverse Events with the Efficacy of Immune Checkpoint Inhibitors

Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma

Contact Info

Product

Resources

About