A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients

Hurkmans, Daan P.; Basak, Edwin A.; Dijk, Thamar van; Mercieca, Darlene; Schreurs, Marco W. J.; Wijkhuijs, Annemarie J.M.; Bins, Sander; Hoop, Esther Oomen–de; Debets, Reno; Joerger, Markus; Odink, Arlette E.; Veldt, Astrid A.M. van der; Leest, Cor H. van der; Aerts, Joachim; Mathijssen, Ron H.J.; Koolen, Stijn L.W.

doi:10.1093/annonc/mdz253.099

Cited by 13 publications

(24 citation statements)

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“…The pharmacology of most of the immune checkpoint inhibitors used in lung cancer lends itself to much less frequent dosing than currently used. 79 The plasma half-lives of atezolizumab, nivolumab, pembrolizumab, and durvalumab are 27, 26.7, 26, and 12 days respectively. Currently, nivolumab can be given at a dose of 480 mg every 4 weeks.…”

Section: Overall Treatment Of Patients With Lung Cancermentioning

confidence: 99%

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic

Dingemans

Soo

Jazieh

et al. 2020

Journal of Thoracic Oncology

103

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The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection currently remain poorly characterized and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause considerable disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary comorbidities are more likely to have increased risk and mortality from coronavirus disease 2019 as one of its common manifestations is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.

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Section: Overall Treatment Of Patients With Lung Cancermentioning

confidence: 99%

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic

Dingemans

Soo

Jazieh

et al. 2020

Journal of Thoracic Oncology

103

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“…18 The apparent E-R relationship sometimes triggered further clinical studies at a higher dose, yet an improved efficacy at a higher dose has not always been confirmed. For example, a positive exposure-efficacy relationship with tremelimumab was observed at 15 mg/kg every 12 weeks, 19 but a later study with a higher dose intensity (10 mg/kg every 4 weeks for 24 week followed by 10 mg/ kg every 12 weeks) failed to confirm a better efficacy. 5,20 Similarly, for trastuzumab, a postmarketing study at a dose higher than the approved dose did not confirm a better response.…”

mentioning

confidence: 99%

“…21 There was also confusion in the literature on whether a higher dose of nivolumab should be considered due to an apparent E-R relationship. [22][23][24] Thus, the apparent E-R relationship for these therapeutic mAbs is not always informative and sometimes can be misleading. The phenomenon is not well understood and has created challenges regarding the dose selection and optimization of these agents.…”

mentioning

confidence: 99%

Characterizing Exposure–Response Relationship for Therapeutic Monoclonal Antibodies in Immuno‐Oncology and Beyond: Challenges, Perspectives, and Prospects

Dai

Vugmeyster

Mangal

2020

Clin Pharma and Therapeutics

111

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Recent data from immuno-oncology clinical studies have shown the exposure-response (E-R) relationship for therapeutic monoclonal antibodies (mAbs) was often confounded by various factors due to the complex interplay of patient characteristics, disease, drug exposure, clearance, and treatment response and presented challenges in characterization and interpretation of E-R analysis. To tackle the challenges, exposure relationships for therapeutic mAbs in immuno-oncology and oncology are reviewed, and a general framework for an integrative understanding of E-R relationship is proposed. In this framework, baseline factors, drug exposure, and treatment response are envisioned to form an interconnected triangle, driving the E-R relationship and underlying three components that compose the apparent relationship: exposure-driven E-R, baseline-driven E-R, and response-driven E-R. Various strategies in data analysis and study design to decouple those components and mitigate the confounding effect are reviewed for their merits and limitations, and a potential roadmap for selection of these strategies is proposed. Specifically, exposure metrics based on a single-dose pharmacokinetic model can be used to mitigate responsedriven E-R, while multivariable analysis and/or case control analysis of data obtained from multiple dose levels in a randomized study may be used to account for the baseline-driven E-R. In this context, the importance of collecting data from multiple dose levels, the role of prognostic factors and predictive factors, the potential utility of clearance at baseline and its change over time, and future directions are discussed.

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“…Several research groups have studied the diagnostic role of donor-derived cell-free DNA for solid organ transplants including kidney, heart, liver and lung. 7 , 14 - 16 Allomap has been studied extensively, and is utilized in clinical practice, although it has not replaced EMB. 17 - 19 Combination of these platforms may provide adequate accuracy to help minimize the need for EMB-based monitoring.…”

Section: Discussionmentioning

confidence: 99%

Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection

Korutla

Reddy

et al. 2020

Transplantation Direct

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Background. Endomyocardial biopsy remains the gold standard for distinguishing types of immunologic injury—acute versus antibody-mediated rejection (AMR). Exosomes are tissue-specific extracellular microvesicles released by many cell types, including transplanted heart. Circulating transplant heart exosomes express donor-specific human leukocyte antigen (HLA) I molecules. As AMR is mediated by antibodies to donor HLAs, we proposed that complement deposition that occurs with AMR at tissue level would also occur on circulating donor heart exosomes. Methods. Plasma exosomes in 4 patients were isolated by column chromatography and ultracentrifugation. Donor heart exosomes were purified using anti-donor HLA I antibody beads and complement C4d protein expression was assessed in this subset as marker for AMR. Results. Three patients had no rejection episodes. Circulating donor heart exosomes showed troponin protein and mRNA expression at all follow-up time points. One patient developed AMR on day 14 endomyocardial biopsy that was treated with rituximab, IVIG/plasmapheresis. Time-specific detection of C4d protein was seen in donor heart exosome subset in this patient, which resolved with treatment. C4d was not seen in other 3 patients’ donor exosomes. Conclusions. Anti-donor HLA I specificity enables characterization of circulating donor heart exosomes in the clinical setting. Further characterization may open the window to noninvasively diagnose rejection type, such as AMR.

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A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients

Cited by 13 publications

References 0 publications

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic

Characterizing Exposure–Response Relationship for Therapeutic Monoclonal Antibodies in Immuno‐Oncology and Beyond: Challenges, Perspectives, and Prospects

Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection

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