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Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

ABSTRACT: The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Moreover, we discuss the currently available data regarding the mechanism of action of immune checkpoint inhibitors and IL-2 analogs in the treatment of COVID-19. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in an elderly melanoma patient.

SUBMITTER: Anastasopoulou A

PROVIDER: S-EPMC9295713 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

Anastasopoulou Amalia A Gkoufa Aikaterini A Diamantopoulos Panagiotis P Kazanas Spyridon S Eliadi Irene I Samarkos Michael M Gogas Helen H

Immunotherapy 20220719 13

The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Mor ...[more]

PMID: 35852114

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Project description:PurposeTherapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma.MethodsA total of 41 previously untreated patients with stage III/IV melanoma received BEMPEG 0.006 mg/kg plus NIVO 360 mg once every 3 weeks for ≤ 2 years; 38 were efficacy-evaluable (≥ 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers.ResultsAt 29.0 months' median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was -78.5% (response-evaluable population); 47.4% (18 of 38 patients) experienced complete clearance of target lesions. Median progression-free survival was 30.9 months (95% CI, 5.3 to not estimable). Median OS was not reached; the 24-month OS rate was 77.0% (95% CI, 60.4 to 87.3). Grade 3 and 4 treatment-related and immune-mediated adverse events occurred in 17.1% (7 of 41) and 4.9% (2 of 41) of patients, respectively. Increased polyfunctional responses in CD8+ and CD4+ T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD8+ polyfunctional strength difference and eosinophils) correlated with treatment response.ConclusionBEMPEG in combination with NIVO was tolerated, with relatively low rates of grade 3 and 4 treatment-related and immune-mediated adverse events. The combination had encouraging antitumor activity in first-line metastatic melanoma, including an extended median progression-free survival. Exploratory analyses associated noninvasive, on-treatment biomarkers with response, before radiologic evidence was observed.

Project description:RationaleWhile checkpoint inhibitors have revolutionized the treatment of melanoma, it is not known whether switching from one monoclonal antibody drug to another one would be justified in the case of a treatment failure. Herein, we report a case illustrating a durable response to pembrolizumab after a failure with nivolumab.Patient concernsA 76-year-old white male noticed an enlarging papular lesion on his neck.DiagnosisMalignant melanoma.InterventionsThe patient underwent surgery in December 2013 and was found to have a B-Rapidly Accelerated Fibrosarcoma (BRAF) V600E mutated melanoma. Treatment with BRAF and MAPK/Erk kinase (MEK) inhibitors along with radiation was initiated. After 1 year, the disease progressed, and the treatment was switched to the cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody, ipilimumab. As the tumor did not respond, the treatment was changed to programmed cell death receptor-1 (PD-1) blockers: nivolumab followed by pembrolizumab. Since the initial diagnosis, the tumor response was monitored by computed tomography (CT) scans. Immunohistochemistry (IHC) was also used for the assessment of programmed death ligand 1 PD-L1) expression in the neck, lung, and spleen lesions.OutcomesThe patient had an initial mixed response to nivolumab, but the disease ultimately progressed as evidenced by new metastases to the spleen, thus the treatment was switched to pembrolizumab. After 46 cycles of treatment, all sites of metastases disappeared, including a substantial shrinkage of the splenic metastasis. To gain understanding about the pharmacological differences between nivolumab and pembrolizumab, the PD-1-ligands interactions and conformational dynamics responsible for the PD-1/PD-L1 checkpoint blockade were investigated. The higher affinity of pembrolizumab might likely arise from a unique and large patch of interactions engaging the C'D loop of PD-1, thus forcing an important motion across the PD-1 immunoreceptor.LessonsIn this case report, we described the tolerance and response of a melanoma patient to a sequence of various agents, including ipilimumab, nivolumab, and pembrolizumab. To the best of our knowledge, this is the first clinical report highlighting differences between PD-1 blockers, as shown by the unexpected and durable response of the tumor to pembrolizumab, after a treatment failure with nivolumab.

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Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

Publications

Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

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