A case of de novo alloimmunisation under daratumumab therapy

Daratumumab (Dara), a therapeutical anti-CD38 monoclonal antibody targeting plasma cells, is known to interfere with antibody screening and crossmatching tests. Initially, extended matching was recommended to avoid alloimmunisation in these patients. While it was clear that alloimmunisation was hard to identify under Dara therapy, it was less clear, whether patients receiving Dara are capable of forming new alloantibodies at all. We report a case of de novo alloimmunisation under Dara therapy.

Antibody screening, differentiation, and direct antiglobulin test (DAT) were performed by gel card technique(Bio-Rad). Dara interference was neutralised by DaraEx® (Inno-train) according to manufacturer"s instructions. The Lutheran a [Lu(a)] antigen was tested using two polyclonal human sera (Bio-Rad, Antitoxin). Red blood cell (RBC) units were crossmatched using DaraEx® and were phenotypically matched for AB0, RhD, extended Rh and K and, after its identification, the antibody; but not for Fya/Fyb, Jka/Jkb, and S/s. The patient"s medical history and transfusion record before referral to our hospital was provided by his hematologist. The patient gave his informed consent with this case report.

A 55 year old male patient received his first Dara dose (day 0) for recurrent multiple myeloma after autologous stem cell transplantation 12 years ago. He had not been transfused during the previous six months. No antibodies (except the Dara interference) were previously reported nor found at admission. Between day +1 and day +26, the patient was administered 25 RBC units, 5 platelet concentrates, und 2 FXIII concentrates. Anti-Lu(a) alloantibodies were first detected 27 days after start of Dara therapy. The DAT was weakly positive (+), but negative for IgG. Lu(a) antigen test showed a mixed-field reaction (2+). There was no clear evidence of delayed hemolysis during intensive care for sepsis, gastrointestinal bleeding, and chronic dialysis.

This case illustrates that patients receiving Dara are indeed capable to form new alloantibodies. Infrequent alloimmunisations under Dara therapy were also recently reported from other countries. It seems reasonable to continue transfusion support for patients under dara therapy with RBC units phenotypically matched for extended Rh and K, but since alloimmunisation is rare, not necessarily matched for Fya/Fyb, Jka/Jkb, and S/s.

AR acknowledges research support (not for the data presented here) by Bio-Rad DiaMed and Sanofi-Aventis.