Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion.

INTRODUCTION: Pembrolizumab, an immune-checkpoint inhibitor, is approved for first-line treatment of metastatic NSCLC in patients with tumours expressing programmed death-ligand 1 (PD-L1) with tumour proportion score (TPS) of ≥50%. We aimed to clarify some uncertainties regarding use of immunotherapy in patients with previous autoimmune (AI) disorders and assess real-world outcomes following treatment completion. METHODS: We performed a retrospective case record review of 82 patients with tumours expressing PD-L1 at TPS ≥ 50% and receiving first-line Pembrolizumab. Survival was estimated using the Kaplan Meier method. RESULTS: After 36.93 months (IQR: 34.37-40.20) median follow-up, median OS was 13.6 months (95% CI 8.9-19.3). There were 10 patients (12%) with AI co-morbidities and there was a trend toward improved median OS for this group versus those without AI comorbidity, 42 months (14.87-NR) versus 10.7 months (7.3-17.8), p = 0.073. Sixteen patients (20%) with nonprogressive disease at 2 years had significantly better median OS compared to those who did not complete 2 years of treatment, NR (42- NR) and 8.7 (5.8-14.1), p < 0.001.Immune related adverse events (irAE) of any grade occurred in 90% of the AI cohort compared with 70.8% of patients without AI comorbidity. Low grade adrenal insufficiency was the only irAE which occurred at a significantly higher rate in the AI group, p = 0.02. CONCLUSION: Patients with previous AI diseases tolerate treatment well, and there is a non-significant trend for improved outcomes in this group. Patients who complete the course of pembrolizumab have significantly better survival outcomes than those who do not.

Tenosynovial giant cell tumor: a case report.

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

Baseline and Dynamic Changes in Hemoglobin Levels Predict Treatment Response and Prognosis in Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: Clinical markers of response in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. This study evaluates the role of Hb as a marker of treatment outcomes in mRCC. PATIENTS AND METHODS: This multicenter retrospective study evaluated 276 patients with mRCC treated with frontline immune checkpoint inhibitor (ICI) therapy, ICI and vascular endothelial growth factor (VEGF) inhibitor (VEGFI) combinations (ICI/VEGFI), or VEGFI monotherapy between 2014 and 2021. Hb levels at baseline, week 6 and 12 and at disease progression or death were recorded. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The association between baseline and dynamic changes in Hb and oncological outcomes was assessed. RESULTS: Thirty-seven percent, 40% and 22% of patients received ICIs, ICI/VEGFI and VEGFI respectively. In patients receiving ICIs, there was a significant increase in Hb amongst responders from baseline to week 12 (P= .02). Amongst patients receiving ICI/VEGFI, there was an increase in Hb from baseline to week 12 which was greater in responders (P< .001). In patients receiving VEGFI monotherapy, responders had a higher Hb at baseline (P= .01), week 6 (P= .04), and week 12 (P= .003). An increase in Hb was a significant independent predictor of progression-free survival amongst patients receiving ICIs (HR 0.40, 95%CI, 0.19-0.83, P= .009). CONCLUSION: Baseline and dynamic changes in Hb are associated with first-line treatment outcomes in patients with mRCC and represent a pragmatic early serological marker.