Balancing Cancer Immunotherapy Efficacy and Toxicity

Johnson, Douglas B.; Jakubovic, Baruch D.; Sibaud, V.; Sise, Meghan E.

doi:10.1016/j.jaip.2020.06.028

Cited by 31 publications

(21 citation statements)

References 86 publications

(106 reference statements)

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“…However, due to the complexity of immunotherapy effects, the large number of complications, and the possibility that GC-induced immunosuppression could counteract the activity of PD-1/PD-L1-blocking drugs, combining the two therapies, when not mandatory, is still problematic. Definitive guidelines on GC treatment concurrent with PD-1/PD-L1 pathway inhibitors are still lacking [ 106 ]. Each neoplasm, given the side effects of immunotherapy, would need a specific protocol for dosage and duration of GC administration.…”

Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Adorisio

Cannarile

Delfino

et al. 2021

Cells

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Programmed cell death protein 1 (PD-1) and its ligands, PD-L1/2, control T cell activation and tolerance. While PD-1 expression is induced upon T cell receptor (TCR) activation or cytokine signaling, PD-L1 is expressed on B cells, antigen presenting cells, and on non-immune tissues, including cancer cells. Importantly, PD-L1 binding inhibits T cell activation. Therefore, the modulation of PD-1/PD-L1 expression on immune cells, both circulating or in a tumor microenvironment and/or on the tumor cell surface, is one mechanism of cancer immune evasion. Therapies that target PD-1/PD-L1, blocking the T cell-cancer cell interaction, have been successful in patients with various types of cancer. Glucocorticoids (GCs) are often administered to manage the side effects of chemo- or immuno-therapy, exerting a wide range of immunosuppressive and anti-inflammatory effects. However, GCs may also have tumor-promoting effects, interfering with therapy. In this review, we examine GC signaling and how it intersects with PD-1/PD-L1 pathways, including a discussion on the potential for GC- and PD-1/PD-L1-targeted therapies to “confuse” the immune system, leading to a cancer cell advantage that counteracts anti-cancer immunotherapy. Therefore, combination therapies should be utilized with an awareness of the potential for opposing effects on the immune system.

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Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Adorisio

Cannarile

Delfino

et al. 2021

Cells

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“…Third, we have no access to toxicity data for patients with PD-L1–negative expression, and such expression is often heterogenous ( 43 ). Balancing the benefit/risk to a specific patient population is always challenging ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

First-Line Treatment Options for PD-L1–Negative Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

Peng

Liang

et al. 2021

Front. Oncol.

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BackgroundFirst-line treatment strategies for programmed death-ligand 1 (PD-L1) negative non-small cell lung cancer (NSCLC) patients include chemotherapy and combination with anti-angiogenesis drugs and/or immune checkpoint inhibitor. We conducted a Bayesian network meta-analysis to evaluate the efficacy of these therapeutic options.MethodsWe included phase III randomized controlled trials comparing two or more treatments in the first-line setting for NSCLC, including data in PD-L1–negative patients. First-line strategies were compared and ranked based on the effectiveness in terms of overall survival (OS) and progression-free survival (PFS). A rank was assigned to each treatment after Markov Chain Monte Carlo analyses.ResultsFourteen trials involving 14 regimens matched our eligibility criteria. For OS, none of the treatment were significantly more effective than chemotherapy. Nivolumab plus ipilimumab plus chemotherapy was probably the best option based on analysis of the treatment ranking (probability = 30.1%). For PFS, nivolumab plus chemotherapy plus bevacizumab, atezolizumab plus chemotherapy plus bevacizumab, and atezolizumab plus chemotherapy were statistically superior to chemotherapy in pairwise comparison. Nivolumab plus chemotherapy plus bevacizumab was likely to be the preferred option based on the analysis of the treatment ranking (probability = 72.9%).ConclusionsNivolumab plus chemotherapy, in combination with angiogenesis inhibition or anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), had maximal benefits for NSCLC patient of PD-L1–negative expression. These findings may facilitate individualized treatment strategies. Safety at an individual patient level should be considered in decision making. Further validation is warranted.

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“…A single target organ is most often affected in mild irAEs, which can occur in 60%–70% of patients accepting a monotherapy of programmed cell death-1 (PD-1)/programmed cell death-Ligand 1 (PD-L1) inhibitor ( 9 ). However, both single and multiple-organs irAEs can be life-threatening.…”

Section: Introductionmentioning

confidence: 99%

Immune-Related Multiple-Organs Injuries Following ICI Treatment With Tislelizumab in an Advanced Non-Small Cell Lung Cancer Patient: A Case Report

et al. 2021

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Immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors (ICIs) can affect almost any organ systems. Multiple-organs irAEs are a rare occurrence which makes its management and treatment very challenging. This is a case report of a 71-year-old man with advanced non-small cell lung cancer (NSCLC) who developed multiple-organs irAEs (lung, muscle, myocardium, liver, and pituitary) after a single cycle (21 days) of the BGB-A317 (Tislelizumab). After more than two months of immunosuppression treatment with glucocorticoids, the tumor and inflammatory lesions in the lung were reduced. The levels of serum creatase, cardiac troponin T (TNT), and hepatic transaminase were also reduced. Four months after the termination of ICI therapy, the lung tumor reappeared in the previous site. This rare case report supplies several experiences in the management of multiple-organs irAEs, including full-scale monitoring of immunological indicators, early differential diagnosis, and prompt glucocorticoid therapy. This patient was not a candidate for the ICI re-challenge therapy due to the number and seriousness of irAEs. Multiple-organs irAEs add complexity to the management, and additional research is needed to develop optimal therapeutic guidelines.

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Balancing Cancer Immunotherapy Efficacy and Toxicity

Cited by 31 publications

References 86 publications

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

First-Line Treatment Options for PD-L1–Negative Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

Immune-Related Multiple-Organs Injuries Following ICI Treatment With Tislelizumab in an Advanced Non-Small Cell Lung Cancer Patient: A Case Report

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