Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary

Brahmer, Julie R.; Lacchetti, Christina; Thompson, John A.

doi:10.1200/jop.18.00005

Cited by 350 publications

(496 citation statements)

References 2 publications

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“…In this reported series, the patients who were treated before these medications were in routine clinical practice tended to have poorer outcomes, including treatment‐related death and colectomy. In the current era, the early and rigorous introduction of immunosuppressive agents in patients not responding to corticosteroids is recommended in many professional society guidelines . By the end of this time period, the participating hospitals had either developed institutional protocols or adhered to professional society guidelines, which promote early administration of immunosuppressive medications for steroid‐refractory irAEs.…”

Section: Discussionmentioning

confidence: 99%

“…In the current era, the early and rigorous introduction of immunosuppressive agents in patients not responding to corticosteroids is recommended in many professional society guidelines. 15,16 By the end of this time period, the participating hospitals had either developed institutional protocols or adhered to professional society guidelines, which promote early administration of immunosuppressive medications for steroid-refractory irAEs. The early identification and treatment of severe irAEs will be essential to limit the potential morbidity and mortality burden for treated patients.…”

Section: Inclusion Of Different Kinds Of Immune Checkpoint Inhibitor mentioning

confidence: 99%

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Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

Burdett

Hsu

Xiong

et al. 2019

Asia-Pac J Clncl Oncology

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Aim To examine the cancer‐specific outcomes for patients who experience immune‐related adverse events requiring immunosuppression beyond corticosteroids. Methods We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune‐related adverse event. Results From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA‐4 inhibitor, four a PD‐1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non‐small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease. Conclusion Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life‐threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer‐specific outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Inclusion Of Different Kinds Of Immune Checkpoint Inhibitor mentioning

confidence: 99%

Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

Burdett

Hsu

Xiong

et al. 2019

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

show abstract

“…Unlike the adverse effects associated with more traditional forms of therapy, such as cytotoxic or molecularly targeted agents, irAEs can be variable in their onset and often require specific management [15,16]. Consensus guidelines from the American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN), and Society for Immunotherapy of Cancer (SITC) provide recommendations for monitoring, diagnosis, and treatment of irAEs [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

A Review of Immune-Mediated Adverse Events in Melanoma

Kennedy

Salama

2019

Oncol Ther

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The use of checkpoint inhibitor-based immunotherapy has transformed the treatment landscape for melanoma as well as many other cancer types. With the ability to potentiate tumor-specific immune responses, these agents can result in durable tumor control. However, this activation of the immune system can lead to a unique constellation of side effects, distinct from other cancer therapies, collectively termed immune-mediated adverse events (irAEs). This review will focus on irAEs and guidelines for management related to the most clinically relevant checkpoint inhibitors, those that target programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4).

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“…Accumulating experience support the use of corticosteroids as first-line treatment of severe immune-related side effects and immunosuppression with, for instance, MMF as second-line [12,13]. Adverse effects and their treatments do not seem to impair the effects of checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

et al. 2020

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Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer, speculated to arise from hepatic progenitor cells, and with a worse prognosis than hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) levels may be one prognostic factor. It has been suggested that checkpoint inhibition might be useful in the treatment of HCC where there is an increased expression of PD-1 and PD-L1 in the microenvironment. Its effect on CHC is unknown. We report a case with a large CHC, which was radically resected, but the 53-yearold female patient subsequently developed pulmonary metastases. Histology demonstrated low-differentiated CHC without microsatellite instability. Treatment with sorafenib was started but was stopped due to angioedema. Under subsequent gemcitabine/cisplatin treatment, the metastatic disease progressed with rising AFP levels. A third-line treatment with pembrolizumab was then started, 2 mg/kg b.w. i.v. every third week for 6 months. This resulted in a radiologically complete remission of the pulmonary metastases and AFP levels were normalized (<10 μg/L) from a level of 1,790 μg/L before treatment. The patient developed immunerelated adverse events (AEs) including diarrhea and hepatitis. These AEs were successfully treated with prednisolone and mycophenolate mofetil, and they were eventually resolved. There are no signs of cancer recurrence neither in the liver nor in the lungs at 33 months after the start of the checkpoint inhibition treatment, and the patient is doing well. Further study is urgently needed on the role of checkpoint inhibition therapy in liver cancer. are responsible for the surgical care and M.P. and L.N. for the oncologic care of the patient. F.A. and J.S. for conception of the study and drafting the manuscript. L.S. is responsible for the pathology examination of the primary liver tumor and pulmonary metastases including histology, immunohistochemistry analyses of MSI. F.H. is responsible for the radiological examinations of the patient. All authors were involved in writing the final manuscript.

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Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary

Cited by 350 publications

References 2 publications

Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

A Review of Immune-Mediated Adverse Events in Melanoma

Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

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