Abstract

Abstract Introduction/Objective Increased expression of CD47 by cancer cells inhibits macrophages' phagocytic activity through CD47-SIRPα interactions, allowing evasion of the innate immune system. Several drugs on the market have been developed to target this interaction, including monoclonal therapeutics and fusion proteins. ALX148 is a genetically engineered SIRPα fusion protein with an inactivated Fc portion. CD47 is expressed highly on red blood cells (RBC), resulting in strong interference in pre-transfusion compatibility testing of patients receiving ALX148. Consequently, trial patients are at increased risk of transfusion-related adverse events or delay of needed transfusion. Few resolutions of ALX148 interference to assess underlying alloantibody development have been reported. One such examiniation demonstrated x6 linear papain-treated RBC adsorptions removed ALX148 interference. This study aimed to replicate these findings. Methods/Case Report Three patients receiving combination ALX148 (dose 6.57-20mg/mL) and Azacitidine therapy with broad-reactive RBC antibody reactivity were selected. High volume alloadsorptions (8:1 RBC:plasma) were performed with papain-treated rr (ccdee) RBCs. Adsorptions were incubated at 37C for 10 minutes. Polyethylene glycol (PEG) was utilized in test tube indirect antiglobulin testing (IAT). Results (if a Case Study enter NA) Initial reactivity strength was 3-4+ at PEG-IAT and saline-IAT with a three-cell screening RBC reagent. Alloadsorbed plasma was non-reactive at IAT with a three-cell screening RBC reagent enhanced by PEG. Drug interference was removed following three times high volume papain-treated alloadsorption. Conclusion Cancer immunotherapies have transformed the standard of care in oncology. Despite the evident clinical success, the medical laboratory has been challenged with adapting to cancer drug therapies capable of causing interference in routine laboratory testing. Clinical trials of ALX148 are associated with interference in pre-transfusion compatibility testing. The use of extended phenotype matching for RBC transfusion can be utilized but incurs additional time and resources. These results suggest high volume linear papain RBC alloadsorptions may be incorporated into antibody resolution for patients receiving ALX148.

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