#OA4-AM25-TU-15 - Daratumumab Administration Results in Durable Reduction of Isohemagglutinin Titers in ABO-Mismatched Bone Marrow Transplant

ABO-mismatched bone marrow transplantation (BMT) presents significant clinical challenges in recipients with high isoagglutinin titers. These can include delayed erythroid engraftment, pure red cell aplasia (PRCA), and increased transfusion requirements. Daratumumab, an anti-CD38 monoclonal antibody, targets plasma cells, the primary source of isoagglutinins, and may offer a novel strategy to mitigate these complications. In this series, we sought to describe how daratumumab was used in three major ABO-mismatched BMT cases to reduce adverse transplant outcomes.

Study

Design/Methods:

 Subjects of any age who received at least one dose of daratumumab for a major or bidirectional ABO-mismatched BMT were eligible for inclusion. Subjects were identified using EMERSE, a local free-text search tool for the electronic medical record. Data collected from each subject’s chart included basic demographic information, other immunosuppressive therapies administered within 30 days of daratumumab, dates and doses of daratumumab administration, and all anti-A1 and anti-B titer results. Only IgM titers were measured following daratumumab infusion due to anti-CD38 interference. Adverse events related to daratumumab were also recorded. A descriptive analysis of the collected variables was performed using Microsoft Excel.

Results/Findings:

Three subjects met the inclusion criteria for the study (Figure 1). Subjects A and B received a single dose of daratumumab and rituximab and underwent therapeutic plasma exchange in the peri-transplant period to address elevated anti-donor isoagglutinin titers (≥128). Despite red blood cell (RBC) reduction, the donor marrow stem cell product infusion resulted in exposure to 41.3 mL and 133.9 mL of incompatible RBCs, respectively. Subject B, who received the larger volume of incompatible RBCs, experienced mild, limited hemolysis and required one RBC transfusion. For subject A, isoagglutinin titers were significantly reduced by Day +30, and for subject B, isoagglutinin titers were suppressed by Day +59. Neither developed PRCA. Subject C received daratumumab on Day +80 for PRCA in the setting of persistently elevated isoagglutinin titers. The subject received 10 total infusions. Titers declined from 8 to 1 after two doses; however, transfusion dependence persisted until Day +124. All three subjects demonstrated a durable reduction in isoagglutinin titers following daratumumab treatment. No infusion-related adverse effects or infectious complications were reported.

Conclusions:

Daratumumab is a promising adjunctive therapy to reduce isoagglutinin titers in the setting of major ABO mismatched BMT. These cases support further investigation with larger, controlled studies to determine the optimal role for daratumumab in the prevention or treatment of immune-mediated phenomena associated with ABO-mismatched BMT.