To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease

Pantuck, Morgan; McDermott, David F.; Drakaki, Alexandra

doi:10.1002/cncr.32326

Cited by 26 publications

(22 citation statements)

References 35 publications

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“…Figure 6 compares the level of autoimmune response for the two immunotherapy options. Consistent with previous experience [21], our model indicates that non-specific therapies may create greater risk for autoimmune disorders than targeted therapies. The autoimmune impact of targeted immunotherapies is much lower, as they are intended to raise the productivity of targeted cells, rather than the overall population of immune system cells.…”

Section: Cancer Treatments and Their Performancesupporting

confidence: 88%

Cancer as a System Dysfunction

Saeed

Ryder

Manning

2021

Systems

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In this paper, we describe a system dynamics model that views cancer as a dysfunction of the cellular system rather than as an ailment of cells. Our experiments with the model replicate the propagation of the ailment and the impacts of the treatments. It presents a concept that deviates from the pervasive view of cancer as a cell malfunction that has led to treatments aiming to destroy the rogue cells. It points to more holistic treatment options aiming at reforming cell interaction so the system can contain the growth of cancer cells. Further research is needed to explore the details for such options.

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Section: Cancer Treatments and Their Performancesupporting

confidence: 88%

Cancer as a System Dysfunction

Saeed

Ryder

Manning

2021

Systems

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“…On the other hand, we did not observe the same favourable association between autoantibody positivity and cancer-related outcomes. Unlike the exclusion criteria applied in most clinical trials [ 8 ], selected patients with autoimmune features could be suitable candidates for receiving ICIs, especially if we apply tools capable of detecting individuals with a problematic risk-benefit ratio. There is still a need to improve our understanding of the relationship among autoimmunity profile, risk of irAEs and ICI efficacy [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Concerning toxicity, though many patients receiving ICIs experience some form of irAEs, which hinder or even prevent ICI administration, predictors of irAEs are not well established [ 6 ]. On the other hand, patients diagnosed with autoimmune diseases, some of which are per se risk factors for malignancy [ 7 ], have been systematically excluded from the pivotal clinical trials relating to ICIs [ 8 ]. Despite this hampering access to ICIs, the available evidence indicates that survival is better in patients who experience irAEs than those who do not [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

et al. 2021

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Background The aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs). Methods We retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor). Results Sixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05). Conclusion Positivity in a readily available autoantibody battery may be associated with the occurrence of irAEs. KEY MESSAGES Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events. Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.

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“…Considering the previously reported data, pre-existence in a patient of an autoimmune disease could be a possible obstacle in the prescription of check-point inhibitor immunotherapy. However, new data suggest that benefits from immunotherapy treatments may outweigh the exacerbation of pre-existing autoimmune disease, especially when the pathology taken into account is not a life-threatening disease such as leukoderma [81].…”

Section: Check-point Inhibitorsmentioning

confidence: 99%

Melanoma and Vitiligo: In Good Company

Failla

Carbone

Fortes

et al. 2019

IJMS

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Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin melanocytes. However, vitiligo has been associated with cutaneous melanoma since the 1970s. Most of the antigens recognized by the immune system are expressed by both melanoma cells and normal melanocytes, explaining why the autoimmune response against melanocytes that led to vitiligo could be also present in melanoma patients. Leukoderma has been also observed as a side effect of melanoma immunotherapy and has always been associated with a favorable prognosis. In this review, we discuss several characteristics of the immune system responses shared by melanoma and vitiligo patients, as well as the significance of occurrence of leukoderma during immunotherapy, with special attention to check-point inhibitors.

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To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease

Cited by 26 publications

References 35 publications

Cancer as a System Dysfunction

Cancer as a System Dysfunction

Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

Melanoma and Vitiligo: In Good Company

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