Multi-Center Real-World Outcomes of Nivolumab Plus Ipilimumab and Chemotherapy in Patients with Metastatic Non-Small-Cell Lung Cancer.

Immune checkpoint inhibitors have become the standard of care in the treatment of metastatic non-small-cell lung cancer (NSCLC). The combination of nivolumab plus ipilimumab and chemotherapy has been shown to improve outcomes in terms of overall survival (OS) and progression-free survival (PFS). The aim of this study was to evaluate the outcomes of metastatic NSCLC treated in routine practice on the treatment regimen of the CheckMate 9LA protocol. Medical records of 58 patients treated at Soroka and Bnai Zion Medical Centers between May 2020 and February 2022 were analyzed. All patients were treated with a regimen of platinum-based chemotherapy combined with immunotherapy of nivolumab every three weeks and ipilimumab every 6 weeks. The patients received 2-3 cycles of chemotherapy according to the physician's choice: platinum-based cisplatin or carboplatin with either pemetrexed or paclitaxel. The median PFS was 10.2 months, longer than that of the 9LA trial (6.7 months). Adenocarcinoma patients exhibited a higher median OS of 13.7 (range 5-33) months than squamous cell carcinoma (SCC) patients at 12.3 (5-20) months and PFS of 10.3 (4-33) months, while squamous cell carcinoma patients had a PFS of 9.2 (4-18) months. Patients whose programmed death ligand-1 (PD-L1) tumor expression level was ≥1% showed a higher median OS than those with PD-L1 expression of less than 1%. Treatment-related adverse events (TRAEs) were reported in 93.1% of patients, mostly grade 1 in severity. The first-line treatment of metastatic NSCLC patients in combination with nivolumab plus ipilimumab and chemotherapy can be given safely in routine clinical practice, with results comparable to those achieved in clinical trials of the regimen.

Cabergoline treatment for recurrent Cushing's disease during pregnancy.

OBJECTIVE: Cushing's disease during pregnancy is associated with an increased risk for maternal and fetal complications. In recurrent Cushing`s disease following transsphenoidal surgery, and when re-operation is not feasible, medical treatment is usually considered. Cabergoline was found to be effective in reducing hypercortisolism in Cushing's disease. Evolving data concerning the safety of cabergoline use during pregnancy show no significant increase in the rate of complications during pregnancy or the postnatal period. METHODS: We report a 29-year-old woman, gravida 0, para 0, with recurrent Cushing`s disease, three years after transsphenoidal resection of pituitary ACTH-secreting macroadenoma. Repeated MRI revealed an empty sella with a small gadolinium-enhancing lesion, suspected to be an adenoma remnant on the medial wall of the right cavernous sinus. As the patient was not willing to undergo repeat surgical intervention, treatment with cabergoline was initiated, with a gradual dose titration up to 3.5 mg/week. Clinical improvement ensued, and 4 months later, she conceived spontaneously. After discussing treatment options with the patient, cabergoline treatment at a dose of 2 mg/week was continued throughout pregnancy. RESULTS: The patient showed complete clinical remission during pregnancy. Consecutive tests of 24-h urinary free cortisol concentration were not found to be elevated. Pregnancy and delivery were uneventful except for mild hypothyroidism observed during the second trimester. At full term the patient delivered a healthy female infant, by an elective cesarean section. CONCLUSION: This case report demonstrates that cabergoline may be an effective and safe therapeutic option for the treatment of Cushing's disease during pregnancy.

Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

BACKGROUND: The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). METHODS: Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. RESULTS: The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. CONCLUSIONS: Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed.