PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study.

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1. RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1+ CTCs (14/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1- CTCs (26.6 months vs. 5.5 months; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1- CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052-1.012; p = .026). CONCLUSION: Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. IMPLICATIONS FOR PRACTICE: The present data suggest that PD-L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings.

An Unusual Presentation of Pyoderma Gangrenosum Leading to Systemic Inflammatory Response Syndrome.

This is a report of an atypical presentation of pyoderma gangrenosum (PG) in a 26-year-old male who had a negative septic screen. The patient had a life-threatening presentation requiring an intensive care unit (ICU) admission for vasopressor support. It was thought that the likely cause of circulatory collapse was an overwhelming cytokine reaction or systemic inflammatory response syndrome (SIRS) secondary to extensive PG lesions rather than septic shock. The patient presented with multiple large ulcers, the largest being 4 cm in diameter on the central chest. He developed fevers and circulatory shock preceding his ICU admission. Microbiological specimens, including blood cultures and wound swabs, were negative for any growth (bacterial, fungal, and tuberculosis). No infective foci could be identified as a cause of hemodynamic instability. During admission, the patient's condition was complicated by multi-organ dysfunction. Wound debridement extending to the deep fascia on the anterior chest, back, bilateral shoulders, and right upper thigh was deemed necessary and performed by the plastic surgery team. Histopathology showed abundant neutrophils but could not confirm an infective process. Overall, the patient made an impressive recovery with almost complete healing of all lesions following oral prednisolone alone. Based on the history and clinical and laboratory findings, a diagnosis of PG complicated by a SIRS was favored. Very few cases of neutrophilic dermatoses have been described in this way. A similar presentation has been described in a 76-year-old female with lower-leg ulcers who developed circulatory shock and required an amputation. Lesions continued to appear despite antibiotics and surgical treatment. Septic screen was negative. She was subsequently diagnosed with PG and recovered rapidly after steroid therapy.

Painful Leg Ulceration in a Poorly Controlled Hypertensive Patient: A Case Report of Martorell Ulcer.

Martorell ulcer is a form of lower limb ulceration, preceded by a small area of excruciating pain. It often appears as a solitary lesion on the outer aspect of the lower limb, and is primarily associated with poorly controlled hypertension and diabetes. Treatment of the ulcer involves awareness and early correct diagnosis, adequate control of blood pressure, management of infection, and wound care. We describe a 77-year-old diabetic and hypertensive woman presenting with excruciating pain in her right lower lateral leg leading to a necrotic ulcer. Serial photographs of the evolution of the lesion and eventual healing of the ulcer are presented.