Adverse events, need for hospitalization and systemic immunosuppression in very older patients (over 80 years) treated with anti-PD-1 for metastatic melanoma

Barailler, H.; Salomon, G.; Dutriaux, Caroline; Prey, S.; Gérard, E.; Dousset, L.; Mertens, C.; Beylot‐Barry, M.; Meyer, Nicolás; Pham‐Ledard, Anne

doi:10.1016/j.jgo.2020.03.003

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…Furthermore, the occurrence of AEs was lower. Immunotherapy seems to be effective and safe for patients over 80 years of age [29], despite the immune senescence and immune system deregulation that affect T cells in the geriatric population [30]. Older patients may have a better response, with a better tolerance than younger patients [31,32].…”

Section: Discussionmentioning

confidence: 99%

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

Bailly-Caillé

Kottler

Morello

et al. 2023

Cancers

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Background: Cemiplimab is a monoclonal antibody targeting the PD-1, and phase II trials have shown its efficacy in the treatment of advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy as a first- or later-line treatment. A synergistic antitumoral response has been demonstrated with concurrent radiotherapy and PD1-immunotherapy. However, no real-life study has demonstrated this effect in advanced cutaneous squamous cell carcinoma. Methods: We conducted a real-life retrospective cohort study to investigate the benefit of concomitant therapy in 33 patients treated with cemiplimab at the University Hospital of Caen, alone (C group) or concomitant to radiotherapy (C/RT group). Our primary objectives were to evaluate the best overall response and objective response rate. Our secondary objectives were the disease control rate, median time to response, progression-free survival, overall survival, clinical benefit of radiotherapy, and safety data. After stopping cemiplimab administration, we performed a follow-up of our patients and performed a descriptive study. Results: We reported an objective response rate of 45.5%, including 47.6% in the cemiplimab group versus 41.6% in the concomitant group. The addition of radiotherapy to cemiplimab enables an earlier clinico-radiological response, with a median duration of 5.5 months in the cemiplimab group versus 3 months in the concomitant therapy group. The response to treatment was prolonged despite discontinuation of cemiplimab, with 91.6% (n = 11/12) and 83.3% (n = 10/12) patients in complete or partial remission at 6 months and 1 year after cessation of cemiplimab and no switch to another oncological treatment, respectively. Radiation therapy also provided a therapeutic effect in 83.3% of the patients in the concomitant group, without increasing the occurrence of adverse events. Conclusions: Our study confirms the efficacy of cemiplimab and radiotherapy in the management of advanced cutaneous squamous cell carcinoma. Concomitant therapy permitted to obtain an earlier radiological response, a beneficial local therapeutic effect of radiotherapy, without any safety alert.

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Section: Discussionmentioning

confidence: 99%

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

Bailly-Caillé

Kottler

Morello

et al. 2023

Cancers

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“…Despite the immune senescence and immune system deregulation that affects antigen-presenting cells, T lymphocytes and effector molecules in the geriatric population [ 34 ], immunotherapy treatment seems to be effective and safe for patients over 80 years of age [ 35 ]. Some researchers have reported that older patients have a better response and fewer irAES than younger patients treated with PD-1 inhibitors [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases

L’Orphelin

Varey

Khammari

et al. 2021

Cancers

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Background: For several decades, PD‐1 has been a target in malignant melanoma (MM). PD‐1 inhibitors (nivolumab, pembrolizumab) and anti‐CTLA‐4 (CD152) (ipilimumab) have revolutionized cancer therapy. PD‐1 and CTLA‐4 inhibition leads to prolonged lymphocyte effects, which explains the cytotoxicity underlying immune‐reaction‐based adverse events (irAEs). Most irAEs occurin the first cycle of treatment at a median of 40 days. IrAEs of any grade have been observed in 68.2% of patients, with 10% of patients experiencing severe grade III/IV irAEs. Data on late‐onset irAEs are lacking. Methods: Data on patients with advanced melanoma (N = 1862) from March 2016 to March 2021 were obtained from the RicMel database, a French national multicentric biobank dedicated to the follow‐up of MM patients. Patients who received anti‐PD‐1 therapy or a combination therapy and experienced grade III‐IV irAEs were selected and analyzed at 7 months, one year and two years after treatment was initiated. Results: Superficial spreading melanoma (SSM) and previous oncological drug administration before immunotherapy are significant risk factors for lateonset irAEs over 2 years after beginning immunotherapy in the univariate and multivariate analysis. The other parameters—sex, mutational status, association of immunotherapy (PD‐1i and CTLA‐4i) and overall response—were not significantly associated with late‐onset irAEs. In our real‐life data study, the median onset time of grade III‐IV irAES was 128 days after the initiation of immune checkpoint inhibitors (ICI) therapy. Conclusions: Our study, using real‐life data, suggests that patients with SSM and those who have received previous oncological treatments are more likely to experience late‐onset grade III‐IV irAES. Further multicentric studies with wider recruitment of patients should be performed to confirm our findings, potentially leading to changes in the recommended treatment for carefully monitored at‐risk patients.

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“…Since there are no effective chemotherapeutic treatments available for metastatic MCC, these immune checkpoint blockade therapies greatly benefitted patients [ 7 , 17 ]. However, these immune-based therapies are not ideal for patients with a medical need to maintain systemic immune suppression [ 23 , 24 ]. These shortcomings demonstrated the need for developing more effective and targeted therapies.…”

Section: Mcpyv and MCCmentioning

confidence: 99%

Merkel cell polyomavirus and associated Merkel cell carcinoma

Yang

You

2022

Tumour Virus Research

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Merkel cell polyomavirus (MCPyV) is a ubiquitous skin infection that can cause Merkel cell carcinoma (MCC), a highly lethal form of skin cancer with a nearly 50% mortality rate. Since the discovery of MCPyV in 2008, great advances have been made to improve our understanding of how the viral encoded oncoproteins contribute to MCC oncogenesis. However, our knowledge of the MCPyV infectious life cycle and its oncogenic mechanisms are still incomplete. The incidence of MCC has tripled over the past two decades, but effective treatments are lacking. Only recently have there been major victories in combatting metastatic MCC with the application of PD-1 immune checkpoint blockade. Still, these immune-based therapies are not ideal for patients with a medical need to maintain systemic immune suppression. As such, a better understanding of MCPyV's oncogenic mechanisms is needed in order to develop more effective and targeted therapies against virus-associated MCC. In this review, we discuss current areas of interest for MCPyV and MCC research and the progress made in elucidating both the natural host of MCPyV infection and the cell of origin for MCC. We also highlight the remaining gaps in our knowledge on the transcriptional regulation of MCPyV, which may be key to understanding and targeting viral oncogenesis for developing future therapies.

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Adverse events, need for hospitalization and systemic immunosuppression in very older patients (over 80 years) treated with anti-PD-1 for metastatic melanoma

Cited by 6 publications

References 10 publications

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

Severe Late-Onset Grade III-IV Adverse Events under Immunotherapy: A Retrospective Study of 79 Cases

Merkel cell polyomavirus and associated Merkel cell carcinoma

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