18F-FDG PET/CT longitudinal studies in patients with advanced metastatic melanoma for response evaluation of combination treatment with vemurafenib and ipilimumab

Sachpekidis, Christos; Kopp‐Schneider, Annette; Hakim-Meibodi, Lara; Dimitrakopoulou-Strauß, Antonia; Hassel, Jessica C.

doi:10.1097/cmr.0000000000000541

Cited by 46 publications

(37 citation statements)

References 40 publications

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“…Interestingly, 8 of 13 of the patients studied with PET/CT demonstrated radiologic signs of arthritis without corresponding clinical symptoms in the respective joints. These findings are in line with recent results of our group in 16 BRAF mutation-positive, metastatic melanoma patients receiving a combination therapy of vemurafenib and ipilimumab [ 42 ]. Seven patients of that cohort developed radiologic signs of irAEs, four of which presenting arthritis without clinical symptoms; importantly, these patients had a significantly longer PFS than those without radiologic irAEs, highlighting a potential relation between the appearance of irAEs signs in PET/CT and the clinical benefit of the treatment [ 24 ].…”

Section: Discussionsupporting

confidence: 92%

Arthralgia Induced by BRAF Inhibitor Therapy in Melanoma Patients

Salzmann

Benesova

Buder‐Bakhaya

et al. 2020

Cancers

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Introduction: BRAF inhibitors (BRAFi), commonly used in BRAF-mutated metastatic melanoma (MM) treatment, frequently cause arthralgia. Although this is one of the most common side effects, it has not been characterized yet. Methods: We retrospectively included all patients treated with BRAFi +/− MEK inhibitors (MEKi) for MM at the National Center for Tumor Diseases (Heidelberg) between 2010 and 2018 and reviewed patient charts for the occurrence and management of arthralgia. The evaluation was supplemented by an analysis of frozen sera. Results: We included 154 patients (63% males); 31% (48/154) of them reported arthralgia with a median onset of 21 days after the start of the therapy. Arthralgia mostly affected small joints (27/36, 75%) and less frequently large joints (19/36, 53%). The most commonly affected joints were in fingers (19/36, 53%), wrists (16/36, 44%), and knees (12/36, 33%). In 67% (24/36) of the patients, arthralgia occurred with a symmetrical polyarthritis, mainly of small joints, resembling the pattern typically observed in patients affected by rheumatoid arthritis (RA), for which a role of the MAPK signaling pathway was previously described. Patients were negative for antinuclear antibodies, anti-citrullinated protein antibodies, and rheumatoid factor; arthritis was visible in 10 of 13 available PET–CT scans. The development of arthralgia was linked to better progression-free survival and overall survival. Conclusion: Arthralgia is a common side effect in patients receiving BRAFi +/− MEKi therapy and often presents a clinical pattern similar to that observed in RA patients. Its occurrence was associated with longer-lasting tumor control.

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Section: Discussionsupporting

confidence: 92%

Arthralgia Induced by BRAF Inhibitor Therapy in Melanoma Patients

Salzmann

Benesova

Buder‐Bakhaya

et al. 2020

Cancers

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“…For example, diffuse 18F-FDG uptake in thyroid or autoimmune thyroiditis has been reported to predict a favorable outcome in DLBCL, treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) [78]. Similar conclusions were reached in other studies, in which patients who developed imaging signs on PET/CT of at least one IrAE (most frequently colitis and arthritis) had a significantly longer progression-free survival (PFS) than those without irAEs [79]. For this reason, it is important to report immune-related findings, even if they are not necessarily associated with clinically significant IrAE.…”

Section: Role Of 18f-fdg Pet/ct In Iraessupporting

confidence: 56%

Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview

Ferrari

Maggialetti

Masi

et al. 2021

JPM

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Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.

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“…[ 18 F]FDG PET/CT is considered the elective imaging technique in detecting metastatic disease in advanced melanoma [19][20][21][22][23]. Moreover, a growing amount of recently published literature has highlighted the potential role of the modality in the prediction of treatment response to ICIs in melanoma, rendering it an attractive tool for the monitoring of immunotherapy [24][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

Sachpekidis

Kopp‐Schneider

Pan

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. Methods Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients’ response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. Results Median follow-up from interim PET/CT was 24.2 months (19.3–41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. Conclusion PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.

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18F-FDG PET/CT longitudinal studies in patients with advanced metastatic melanoma for response evaluation of combination treatment with vemurafenib and ipilimumab

Cited by 46 publications

References 40 publications

Arthralgia Induced by BRAF Inhibitor Therapy in Melanoma Patients

Arthralgia Induced by BRAF Inhibitor Therapy in Melanoma Patients

Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

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