(P-IG-10) Novel Interference of AK117 Antibody Therapy with Some Automated Gel Antibody Screen Platforms

Background/Case Studies: Monoclonal antibody (MOAB) immunotherapy is integral to oncologic treatment; however, some MOABs can interfere with pre-transfusion compatibility testing. A novel anti-CD47 MOAB, AK117, does not cause in vivo RBC hemagglutination, but anecdotal experience suggested that it interfered with indirect immunohematology testing in vitro. The goal of this study was to compile multi-institutional practices with AK117 interference and share blood bank protocols addressing pretransfusion compatibility challenges with this drug.
Study

Design/Methods: A double-blind, randomized controlled trial of AK117 therapy was conducted at multiple medical centers (n=3). At each site, EDTA patient samples were initially tested using gel card platforms (platforms used: Grifols Diagnostics, Los Angeles, CA; Ortho Clinical Diagnostics, Raritan, NJ). Results were compared with historical data, and patient histories were retrieved from the electronic medical record.
Results/Findings: Among enrolled patients, ABO and Rh(D) typing were consistent with historical data in all cases, but a total of 8 subjects across sites demonstrated pan-reactivity (2+ to 3+ reactivity) in gel-based indirect antibody testing; none of these subjects demonstrated prior allo- or autoimmunization per available records. For cases showing pan-reactivity in automated gel testing, one center transitioned to manual tube testing with low ionic strength saline (LISS) enhancement, while two centers switched to manual tube testing with polyethylene glycol (PEG) enhancement. In all eight cases, pan-reactivity resolved with a transition to LISS- or PEG-based manual tube testing allowing alloantibodies to be determined. Notably, DATs were negative with polyspecific anti-sera in all cases. A generic comment about inconclusive reactivity was entered for all patients to prevent unblinding of clinical study personnel.

Conclusions: We report a novel interference of the anti-CD47 MOAB AK117, which was associated with pan-reactivity in indirect antiglobulin assays done via select commercial automated gel platforms; this interference was mitigated by manual testing methods. It is important for the transfusion community to be aware of this interference for AK117, which was unexpected given the lack of in vivo agglutination with this new MOAB. Moreover, the approach outlined herein should provide a useful work-around for other centers who may encounter patients/subjects demonstrating this same interference.