Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune-related adverse events after immune checkpoint inhibitor therapy.

AIM: To examine the cancer-specific outcomes for patients who experience immune-related adverse events requiring immunosuppression beyond corticosteroids. METHODS: We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune-related adverse event. RESULTS: From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA-4 inhibitor, four a PD-1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non-small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease. CONCLUSION: Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life-threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer-specific outcomes.

Acidolysis-dominated pretreatment elevates distillation yield and impacts composition, antioxidant and antifungal activities of essential oil from Cuminum cyminum seeds.

Proper pretreatment of herbal material containing essential oils (EOs) could enhance its volatile components release through either removing physical barriers or conquering chemical bonds and thereby improve hydrodistillation yield. In this regard, a trial pretreatment including pulverization, enzymolysis, short time microwave irradiation and acidolysis of Cuminum cyminum seeds was integrated into the essential oil (EO) preparation to elevate the EO yield. On the basis of Plackett-Burman design analysis, three parameters (acidolysis duration, HCl concentration of acidolysis and sieving mesh) were significant for the EO preparation. Box-Behnken design based optimization of the remaining factors concluded that the optimal pretreatment was pulverizing the seeds to 40 mesh and implementing 45 min acidolysis in 2.5 M L-1 HCl wherein the predicted EO yield of 3.78% was close to that of the experimental value 3.86%. This pretreatment produced an EO yield increase of 50.78% over the control sample of raw seeds (2.56%). In total 53 components were identified in the acidolysis-pretreated cumin EO (AEO) whilst 47 components were identified in the control cumin EO (CEO). In both AEO and CEO, cuminaldehyde was the predominant common component, but the AEO contained more phenols (0.51% vs. 0.18%) and alcohols (7.76% vs. 0.18%) than the CEO did. The compositional features gave the AEO mightier antioxidant potency and stronger antifungal efficacy against four postharvest fungi, viz. Alternaria alternata, Penicillium expansum, Trichothecium roseum and Fusarium sulphureum, as compared with the situations of CEO. In conclusion, the pretreatment elevates the hydrodistillation yield, modifies the EO chemical profiles and confers stronger antioxidant and antifungal activities upon cumin EO.