Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab

Menzies, Alexander M.; Johnson, Douglas B.; Ramanujam, S.; Atkinson, Victoria; Wong, Annie; Park, John J.; McQuade, Jennifer L.; Shoushtari, Alexander N.; Tsai, Katy K.; Eroglu, Zeynep; Klein, Oliver; Hassel, Jessica C.; Sosman, Jeffrey A.; Guminski, Alexander; Sullivan, Ryan J.; Ribas, Antoni; Carlino, Matteo S.; Davies, Michael A.; Sandhu, Shahneen; Long, Georgina V.

doi:10.1093/annonc/mdw443

Cited by 687 publications

(605 citation statements)

References 17 publications

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“…It should be noted that most clinical trials allowed systemic treatment with low-dose corticosteroids (≤10 mg of prednisolone or equivalent). Patients requiring regular high-dose corticosteroid or immunosuppression respond less frequently to immunotherapy [90]. If possible, treating physicians should try and reduce the steroid dose to prednisone ≤10 mg daily (or equivalent) before commencement of anti-PD-1/PD-L1 therapy, to see if the patient is able to tolerate it.…”

Section: The Use Of Single-agent Anti-pd-1/pd-l1 Therapies In Clinicamentioning

confidence: 99%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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Section: The Use Of Single-agent Anti-pd-1/pd-l1 Therapies In Clinicamentioning

confidence: 99%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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“…However, as the use of immunotherapy continues to expand into a broader, real-world population, patients with preexisting autoimmune disorders or immune-mediated adverse events (imAEs) from prior immunotherapy are being considered [107,108]. In one study, the use of the PD-1 blockers pembrolizumab or nivolumab in 119 patients with advanced melanoma and preexisting autoimmune disorders and/or imAEs from prior ipilimumab monotherapy resulted in an ORR of 37%, although approximately 10% of patients discontinued treatment because of imAEs [108].…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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“…26,27 In addition, 38% of patients with a preexisting autoimmune disorder experienced a flair up of it while on ipilimumab; however, most were considered mild. 28 For patients with chronic infections, the theory, several case series, a retrospective study, and a small trial indicate overall safety and may, in fact, be an avenue for future treatment. 29 -34 However, data are currently limited for both patients with chronic infection and autoimmune disorders and more study is warranted.…”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%