LONG-TERM SURVIVAL IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE TREATED WITH INTRATHECAL INTERLEUKIN-2

BACKGROUND: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis and a paucity of effective treatment options. We assessed the safety and efficacy of intrathecal interleukin-2 (IT IL-2) in metastatic melanoma patients with LMD. METHODS: We reviewed the outcomes of 43 consecutive metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug Study. All patients had evidence of LMD based on cerebrospinal fluid (CSF) cytology, radiology, and/or surgical pathology. IL-2 at a dose of 1.2 mIU was administered intrathecally via Ommaya reservoir up to 5 times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1 to 3 months thereafter. RESULTS: The median age of the patients was 46.7 years (range 18-71); 32 (74%) were male; 31 (72%) had positive CSF cytology, and 39 (91%) had radiographic evidence of LMD. Median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 4.7-16.3 months), with 1-, 2-, and 5-year OS rates of 36%, 26%, and 13%. The presence of neurological symptoms (HR 2.1, p=0.03), positive baseline CSF cytology (HR 4.1, p=0.001) and concomitant use of targeted therapy (HR 3.0, p=0.02) were associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure. There were no treatment-related deaths. CONCLUSION: IT IL-2 treatment is safe and achieves long-term survival in a subset of metastatic melanoma patients with LMD

Melanoma central nervous system metastases: current approaches, challenges, and opportunities

Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area

Dermatomyositis associated with nivolumab therapy for melanoma: a case report and review of the literature

We present a rare case of dermatomyositis associated with nivolumab therapy for melanoma. Nivolumab is an immune checkpoint inhibitor that blocks the programmed death-1 (PD1) receptor and has a number of associated immunotherapy related adverse events. Although most are T-cell mediated, some are antibody mediated mimics of classical autoimmune diseases. We review the characteristics of other cases of anti-PD1 associated dermatomyositis and the recent literature to better understand how to classify and treat this challenging immunotherapy related adverse event

Dermatomyositis associated with nivolumab therapy for melanoma: a case report and review of the literature

We present a rare case of dermatomyositis associated with nivolumab therapy for melanoma. Nivolumab is an immune checkpoint inhibitor that blocks the programmed death-1 (PD1) receptor and has a number of associated immunotherapy related adverse events. Although most are T-cell mediated, some are antibody mediated mimics of classical autoimmune diseases. We review the characteristics of other cases of anti-PD1 associated dermatomyositis and the recent literature to better understand how to classify and treat this challenging immunotherapy related adverse event

Management of metastatic cutaneous melanoma: updates in clinical practice

In recent years, several drugs have been approved for the treatment of patients with metastatic cutaneous melanoma, completely reshaping the landscape of this aggressive disease. Immune therapy with cytotoxic T-lymphocyte antigen 4 and programmed cell death-1 inhibitors yielded significant and durable responses, achieving long-term disease control in up to 40% of the patients. BRAF inhibitors (BRAFi), in combination with MEK inhibitors, also resulted in improved overall survival compared with single-agent BRAFi in patients with BRAFV600 -mutated metastatic melanoma. The optimized sequencing and duration of treatment, however, is yet to be found. In this article, we thoroughly review current data and discuss how to best sequence the various treatment modalities available at present, based on four distinct clinical presentations commonly seen in clinic. In addition, we review treatment options beyond checkpoint inhibitors and targeted therapy, which may be required by patients failing such effective treatments

Interstitial granulomatous dermatitis and concurrent immunotherapy associated encephalitis with nivolumab and ipilimumab

Immune-related adverse events (irAEs) are common in patients receiving immune checkpoint inhibitors for metastatic melanoma and other advanced malignancies. Cutaneous, gastrointestinal, and endocrine (thyroid) irAEs are most prevalent, whereas neurologic irAEs are rare. We present a 73-year-old man with dementia and metastatic melanoma who developed immunotherapy-associated encephalitis and subsequently, interstitial granulomatous dermatitis with nivolumab/ipilimumab. High-dose corticosteroids successfully treated both conditions, though he never regained his baseline mental status. We review the literature on interstitial granulomatous dermatitis and encephalitis with immunotherapy

Primary Pineal Melanoma With Leptomeningeal Carcinomatosis

Pineal region tumors commonly present with features of increased intracranial pressure such as headache, nausea, and vomiting due to obstructive hydrocephalus. Parinaud syndrome is also common

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

Background Immune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these invasive procedures frequently can become cumbersome. We sought to assess the role of fecal calprotectin (FC) concentration as a non-invasive biomarker of endoscopic or histologic remission.Methods We performed a retrospective study of patients with IMDC who were tested for FC at IMDC onset and after IMDC treatment between June 2016 and March 2020. Patient demographics, clinical variables, and FC data were collected and analyzed to determine the optimal cut-off FC concentration to predict endoscopic and histologic remission.Results Our sample comprised 77 patients with a median age of 62 years; 66% were male and 94% were Caucasian. Sixty-five patients (84%) achieved clinical remission, 46 (60%) achieved endoscopic remission, and 24 (31%) achieved histologic remission after IMDC treatment. FC concentrations decreased from the time of IMDC onset to the end of treatment (p<0.001). High FC concentrations were associated with evident endoscopic inflammation (p=0.003) and acute/chronic active colitis (p=0.025) which positively correlated with the Mayo Endoscopic Subscore (r=0.615, p=0.001) at the time of IMDC onset. In patients who achieved endoscopic remission after treatment, a significantly lower FC concentration was observed at IMDC onset (p=0.006) and after treatment (p<0.001) compared with those without endoscopic remission. The cut-off FC concentration to predict endoscopic remission was ≤116 μg/g and for histologic remission ≤80 μg/g; these cut-offs had optimal specificity (94% and 85%, respectively) and positive predictive value (0.91 and 0.38, respectively).Conclusions FC concentration may serve as a non-invasive biomarker to predict endoscopic and histologic remission in patients receiving treatment for IMDC, minimizing the need for frequent invasive endoscopies. Future prospective studies are needed to provide further insight on the role of this marker in disease surveillance