Risk of cumulative toxicity after complete melanoma response with pembrolizumab

Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

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“…We also discuss the consequences of the CPI response in terms of metabolic changes (Table 4). [188][189][190][191]…”

Section: Effect Of Metabolic Disorders On Cpi Treatmentmentioning

confidence: 99%

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Deshpande

Sharma

Watabe

2020

Cancers

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“…In the registrative phase-III trials, PD-1 blockers were administered for up to two years or longer until unacceptable AEs [ 1 , 5 , 41 , 42 ]. Interestingly, durable tumor responses have also been observed after the early discontinuation (<2 years) of PD-1 blockade [ 1 , 6 , 8 ], not only in patients who achieved a CR [ 9 ] but also in patients with a PR or SD [ 1 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…In clinical trials, anti-PD-1 antibodies are typically administered continuously over 2 years or until reaching a progression of the disease or unacceptable toxicity. In daily practice, treatment is often discontinued due to treatment-limiting toxicity (TLT) or electively, several months to years following a major tumor response [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Checkpoint Inhibitors Immunotherapy in Metastatic Melanoma: When to Stop Treatment?

2022

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Background: Immune checkpoint inhibition (ICI) has significantly improved the survival of metastatic melanoma (MM) with a significant proportion of patients obtaining long-lasting responses. However, ICI also exposes patients to new, heavy, and sometimes irreversible toxicities. Thus, identifying the minimal amount of treatment time is extremely urgent. Methods: We researched English peer-reviewed literature from electronic databases (MEDLINE and PubMed) until July 2022 with the aim of evaluating the clinical outcomes after the cessation of ICI therapy due to elective study plans, clinician–patient sharing, and adverse events. Results: Although most of the data are from retrospective studies, considering that most patients with major responses maintain it after treatment cessation, it is proposed that for complete response (CR)/near CR, a further six months of therapy after best response may be considered enough. For partial response (PR) or stable disease (SD), treatment must be continued for at least 2 years and, in some cases, indefinitely, based on residual disease, the patient’s will, and the toxic profile. Of note, in spite of the best response, 25–30% of patients relapsed, and, when retreated, responded far less than in front-line treatment. Conclusions: Most of the data being from retrospective and heterogeneous experiences, their grade of evidence is limited and no consensus has been reached on the optimal treatment duration. Controlled prospective studies are needed.

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“…The incidence of these immune-related adverse events (irAEs) tends to increase slowly with continued exposure to anti-PD1 therapy. Most irAEs related to PD1 blockade appear during the first 6 months of treatment (7,8). In one study, the incidence of AEs involving the use of pembrolizumab was 12%.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Toxicity of Pembrolizumab in Pediatric Metastatic Recurrent Melanoma

Marjańska

Gałązka

Marjanski³

et al. 2019

Anticancer Res

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Background/Aim: Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. Case Report: We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. Conclusion: Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12months of follow-up, patient remains in complete remission.

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Risk of cumulative toxicity after complete melanoma response with pembrolizumab

Cited by 5 publications

References 21 publications

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Checkpoint Inhibitors Immunotherapy in Metastatic Melanoma: When to Stop Treatment?

Efficacy and Toxicity of Pembrolizumab in Pediatric Metastatic Recurrent Melanoma

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