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Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature., Methods: Sixty patients with steroid-refractory aGVHD were analyzed. The primary objective was to determine the overall response rate (ORR) for CCBT. Secondary outcomes included non-relapse mortality (NRM) and overall survival (OS)., Results: ORR for CCBT at day 7, 14, and 28 were 28.3% (17/60; CR 5.0%/PR 23%), 38.3% (23/60; CR 11.3%/PR 27%), and 38.3% (23/60; CR 23.3%/PR 15%), respectively. Patients who received ruxolitinib prior to CCBT had lower ORR (25% CR = 15%/PR = 10%) compared to those who did not (47.5% CR = 27.5%/PR = 20%). In patients with and without ruxolitinib initiated prior to CCBT, NRM at 6 months was 60% (95% CI, 34.5-78) and 47.5% (95% CI, 31-62), while OS at 12 months was 30% (95% CI, 12-50) vs. 40% (95% CI, 25-55), respectively., Conclusions: CCBT has shown potential efficacy in steroid-refractory GI aGvHD, and given the observed ORR when used as second-line therapy, CCBT could serve as an acceptable alternative for patients who are ruxolitinib-intolerant. Ruxolitinib-refractory GI GvHD remains an area of unmet need and CCBT can provide salvage therapy for some patients.

Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies., Competing Interests: Vincent Chung: Celgene, speakers bureau; Ipsen and Five Prime Therapeutics, advisory board.