International multicentre evaluation of a new anti-idiotypic anti-daratumumab for resolving pre-transfusion...

Daratumumab, a therapeutic human anti-CD38 monoclonal antibody, improves multiple myeloma outcomes but interferes with pre-transfusion testing by binding CD38 on reagent red blood cells (RBCs), potentially masking clinically significant alloantibodies. This study aimed to evaluate the effectiveness of a novel high-affinity anti-idiotypic anti-daratumumab reagent in neutralizing daratumumab interference while preserving RBC alloantibody detection and ensuring compatibility with routine transfusion laboratory workflows.

A non-interventional, multicentre study across 28 transfusion laboratories in 15 countries evaluated a novel anti-idiotypic anti-daratumumab reagent (DaraClear). In total, 443 daratumumab-containing plasma samples and 197 RBC alloantibody-containing samples were tested. All samples were initially tested at 10% (v/v), with stepwise escalation to 20% and 30% only if neutralization was incomplete. Neutralization efficiency, antibody detection, cross-match resolution and workflow integration were assessed, alongside comparisons with dithiothreitol (DTT), papain, trypsin and DaraEx.

Daratumumab interference was neutralized in 99.5% of samples, with 86.2% resolved using the 10% protocol. Detection of 190/197 RBC antibodies (96.4%) was preserved, including weak/low-titre antibodies. Neutralization was superior to DTT (93.3%), papain/trypsin (84.9%) and DaraEx (68.4%; all p < 0.0001). Titration studies confirmed efficacy across various ranges of daratumumab titres. The reagent integrated seamlessly into workflows, remained stable over time and avoided RBC modification.

Daratumumab interference was efficiently neutralized while preserving alloantibody detection. The robust performance and workflow compatibility provide a practical solution for pre-transfusion testing in daratumumab-treated patients, supporting safe and timely transfusions with reduced laboratory burden.