Reconsider radiation exposure from imaging during immune checkpoint inhibitor trials to reduce risk of secondary cancers in long-term survivors?

ObjectiveWe sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies.MethodsWe conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response.ResultsSixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response).ConclusionICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.

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Measuring the long-term “tail of curve” survival benefits in oncology trials: A comparison of the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2585 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2585-2585

Author(s):

Louis Everest ◽

Monica Shah ◽

Kelvin K. Chan

Keyword(s):

Immune Checkpoint ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Survival Curve ◽

Kappa Statistic ◽

Term Survival ◽

Long Term Survival ◽

Anti Cancer

2585 Background: Recently, anti-cancer agents have generated excitement due to their capacity to preserve long-term survival in some patients, represented by a “tail of the survival curve”. However, as traditional measures of clinical benefit may not accurately capture long-term survival, amendments to various valuation frameworks have been proposed to capture this benefit. The purpose of this study was to determine how frequently immune checkpoint inhibitor vs. non-immune checkpoint inhibitor anti-cancer agents, displayed trends of long-term survival, as defined by the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), as well as to analyze the degree of agreement between ASCO and ESMO frameworks. Methods: Anti-cancer agents from phase II or III randomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approval by the Food and Drug Administration (FDA) between January 2011 and March 2018 were identified. Data required for ASCO-VF and ESMO-MCBS were extracted. Difference in how often long-term survival bonuses were awarded were calculated in all RCTs, as well as immune checkpoint inhibitor and non-immune checkpoint inhibitor RCTs individually. Cohen’s Kappa statistic was calculated to evaluate agreement between ASCO-VF and ESMO-MCBS. Results: 100 RCTs were analyzed. RCTs were awarded ASCO-VF version 2 (v2) “tail of the curve” bonuses more often than ESMO-MCBS version 1.1 (v1.1) “immunotherapy-triggered” long-term plateau adjustments (45% vs. 2.6%). Comparing to non-immune checkpoint inhibitor RCTs, immune checkpoint inhibitor RCTs were not more likely to receive ASCO-VF v2 bonuses/ESMO-MCBS v1.1 adjustments (p = 0.32/ p = 0.40). Long-term survival agreement between the two frameworks was poor (kappa: 0.01; p = 0.50). Conclusions: The ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement in order to accurately capture the benefit of long-term survival or immune checkpoint inhibitor and non-immune checkpoint inhibitor agents may not preserve substantially different long-term survival populations.

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P8‐103: Real world long‐term survival in patients with non‐small cell lung cancer treated with immune checkpoint inhibitor monotherapy

Respirology ◽

10.1111/resp.14150_615 ◽

2021 ◽

Vol 26 (S3) ◽

pp. 328-329

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Real World ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Small Cell ◽

Small Cell Lung ◽

Term Survival

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A long-term lung cancer survivor with cancer-associated thromboembolism with subcutaneous heparin therapy and an immune checkpoint inhibitor

Nosotchu ◽

10.3995/jstroke.10955 ◽

2021 ◽

Author(s):

Sadahisa Okamoto ◽

Susumu Hirosako ◽

Daisuke Sueta ◽

Kenichi Tsujita ◽

Hirotsugu Kohrogi

Keyword(s):

Lung Cancer ◽

Cancer Survivor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Heparin Therapy ◽

Subcutaneous Heparin ◽

Lung Cancer Survivor

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Cures with B-Raf inhibitors as single agents in metastatic B-Raf mutated melanoma: Curb your enthusiasm?

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220975079 ◽

2020 ◽

pp. 107815522097507

Author(s):

Constantin A Dasanu

Keyword(s):

Radiation Therapy ◽

Malignant Melanoma ◽

Clinical Outcome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Inhibitor Therapy ◽

Checkpoint Inhibitor Therapy ◽

Favorable Clinical Outcome

Development of brain metastases during treatment with B-raf/MEK inhibitors for malignant melanoma tends to be more frequent than during immune checkpoint inhibitor therapy. Long-term responders to B-Raf inhibitors with or without MEK inhibition should be monitored very closely clinico-radiologically for a potential relapse. In addition to surgery and/or radiation therapy, single or dual immune checkpoint inhibitor therapy should be started without delay in this setting to ensure a favorable clinical outcome.

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Biomarkers of immune checkpoint inhibitor efficacy in cancer

Current Oncology ◽

10.3747/co.27.5549 ◽

2019 ◽

Vol 27 (S2) ◽

Cited By ~ 2

Author(s):

D. E. Meyers ◽

S. Banerji

Keyword(s):

Patient Outcomes ◽

Immune Checkpoint ◽

Immune Modulation ◽

Urothelial Cancer ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Cell Cancer ◽

Small Cell Lung ◽

Cell Mediated Immune Response

Immune checkpoint inhibitor–based therapies that target ctla-4, PD-1, or the PD-1 ligand PD-L1 have received approval in Canada and many parts of the world for the treatment of melanoma, renal cell cancer, urothelial cancer, classical Hodgkin lymphoma, and non-small-cell lung cancer. However only a small proportion of patients derive long-term clinical benefit. Here, we describe the biomarkers associated with the complex relationship between tumour-related immune stimulus, T cell–mediated immune response, and immune modulation of the microenvironment that can help to predict improved patient outcomes.

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IMMU-21. THE COMBINATION OF DELTA-24-ACT WITH AN IMMUNE CHECKPOINT INHIBITOR RESULTS IN ANTI-GLIOMA EFFECT AND IMMUNE MEMORY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.451 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii109-ii109

Author(s):

Montserrat Puigdelloses ◽

Virginia Laspidea ◽

Marc Garcia-Moure ◽

Daniel De la Nava ◽

Dolores Hambardzumyan ◽

...

Keyword(s):

Immune Checkpoint Inhibitor ◽

Immune Cell ◽

Checkpoint Inhibitor ◽

Immune Memory ◽

Long Term Survivors ◽

Anti Tumour Effect ◽

Murine Glioma

Abstract Oncolytic viruses have become promising therapeutic candidates to treat gliomas. Our group has developed Delta-24-ACT, an oncolytic adenovirus armed with the positive costimulatory ligand 4-1BBL which is capable to trigger the activation of T cells and thereby increase their antitumor immune response. Here we evaluate the anti-glioma effect of Delta-24-ACT alone or in combination with an immune checkpoint inhibitor. We observed that Delta-24-ACT was able to infect and kill murine glioma (GL261-5 and CT-2A) and also human glioma cell lines (U87-MG and U251-MG), while maintaining its replication in the latter. Of importance, Delta-24-ACT infection resulted in 4-1BBL expression on the membrane of glioma cells. Moreover, this ligand was functional and was able to stimulate CD8 lymphocytes in vitro, suggesting the potential of Delta-24-ACT to trigger an effective immune response. Furthermore, in vivo Delta-24-ACT showed anti-tumour effect in two murine glioma models by significantly increasing the median survival time and leading to long-term survivors. Mechanistic studies demonstrated an increase of the T cell infiltration and the activation of different immune cell populations by flow cytometry and a decrease of proliferative cells and tumour vessels by immunohistochemistry on FFPE brain samples. Importantly, the infiltrating lymphocytes also showed signs of exhaustion increasing the amount of IL-10 and the expression of PD-1. To overcome this exhaustion we combined Delta-24-ACT with an anti-PD-1 antibody. Evaluation of this combination in vivo further increased the median survival time of treated tumor-bearing mice and resulted in 50% long-term survivors. Rechallenge studies with the same cell line showed that combination treatment effectively protected these animals of developing tumors and therefore, the acquisition of immune memory. In summary, our data demonstrated that Delta-24-ACT induces a potent anti-tumour effect in vitro and in vivo as a result of the recruitment of immune cell populations modulating the immunosuppressive tumour microenvironment of glioma.

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Long-term immune-related adverse events after discontinuation of immunotherapy

Immunotherapy ◽

10.2217/imt-2020-0320 ◽

2021 ◽

Author(s):

Karoline Horisberger ◽

Carmen Portenkirchner ◽

Andreas Rickenbacher ◽

Luc Biedermann ◽

Christoph Gubler ◽

...

Keyword(s):

Side Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Late Onset ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Symptomatic Therapy ◽

Checkpoint Inhibitor Therapy ◽

Severe Colitis

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and pembrolizumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

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