Toxicities in immunotherapy: Can they predict response?

Prior, Lisa; Harrold, Emily; O’Leary, Connor; Nugent, Killian; Gleeson, Jack Patrick; Watson, Geoffrey Alan; Lim, Marvin; Kelly, Deirdre; McCaffrey, John; Kelly, Catherine M.

doi:10.1200/jco.2016.34.15_suppl.e14534

Cited by 11 publications

(9 citation statements)

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“…While several prior studies have suggested an association between the development of irAEs and clinical response in melanoma patients treated with checkpoint blockade, most were with the cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) inhibitor ipilimumab. For example, a recent study showed that melanoma patients who developed grade 3 toxicities requiring steroid treatment while being treated with ipilimumab had higher response rates and a longer median duration of response . Two other studies in melanoma patients treated with PD‐1 inhibitors have had similar results demonstrating that cutaneous irAEs were associated with a better treatment response .…”

Section: Discussionmentioning

confidence: 96%

Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

et al. 2017

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This study evaluated whether the development of immune-related adverse events in non-melanoma patients treated with programmed cell death 1 checkpoint inhibitors correlates with improved clinical outcomes. The results indicate that for a subset of patients, in particular those with low-grade immune-related adverse events, immune-related adverse events predicted for an improved response rate and longer time to next therapy or death.

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Section: Discussionmentioning

confidence: 96%

Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

et al. 2017

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“…Interestingly, a recent study has suggested a correlation between grade 3 or 4 immunotherapy related adverse events (irAEs) and the degree of durable response. Patients with advanced melanoma treated with ipilimumab who experienced grade 3 toxicities requiring steroids were found to have higher response rates to therapy and a longer median duration of response [ 13 ]. It was postulated by the investigators that these toxicities may reflect increased immunotherapy activity in melanoma, and thus as a result explaining the improved patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

Albandar

Fuqua

Albandar

et al. 2021

Cancers

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Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.

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“…In the future, molecular characterization may guide us. In malignant melanoma patients, treated with Ipilimumab, development of grade-3 toxicities has been shown to correlate with higher response rates and a longer median duration of response [3]. Our patient experienced significant toxicity with immunotherapy.…”

Section: Discussionmentioning

confidence: 77%

“…When the ligands PD-L1 and PD-L2 bind to the PD-1 receptor, it leads to inhibition of the cellular immune response [2]. Tumour cells can exploit this pathway by upregulating PD-L1 to escape immune surveillance [3]. Studies have shown that increased PD-L1 expression is associated with a poor prognosis in renal-cell carcinoma (RCC) [2].…”

Section: Introductionmentioning

confidence: 99%

One dose of immunotherapy leading to an exceptional and durable response in a patient with metastatic renal cell carcinoma

Wade

Hilman

2019

Oxford Medical Case Reports

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A 72-year-old man with metastatic clear cell renal carcinoma, who had progressed after previous treatment with Sunitinib and Axitinib, was given one dose of immunotherapy. He was initially unwell after treatment with fever, shortness of breath, chest pain and raised inflammatory markers. Following this he elected not to have any further immunotherapy. Before the treatment he had multiple pulmonary metastases and hilar and mediastinal lymph nodes on chest X-ray and suffered with a persistent cough. Chest X-ray 10 months after treatment showed normal appearances and his cough had largely resolved. The patient initially declined repeat computed tomography imaging but agreed to it 2 years after the immunotherapy, the results showed a maintained response. Some patients with renal cell carcinoma show a durable response to immunotherapy but we are not aware of other published cases where a patient has shown such a dramatic and sustained response to one dose.

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Toxicities in immunotherapy: Can they predict response?

Cited by 11 publications

References 0 publications

Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

One dose of immunotherapy leading to an exceptional and durable response in a patient with metastatic renal cell carcinoma

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