Daratumumab Overcome Platelet Transfusion Refractoriness in Patients with Aplastic Anemia: A Pilot Trail

Introduction

Platelet transfusion refractoriness (PTR) represents a significant clinical challenge, markedly elevating the risk of hemorrhagic mortality in some patients with transfusion-dependent aplastic anemia. There is an urgent need for effective therapeutic strategies to enhance platelet transfusion responsiveness, beyond the administration of repeated platelet transfusions.

Methods

We conducted a single-arm, single-center, prospective pilot study involving patients with aplastic anemia who exhibited platelet transfusion refractoriness, as evidenced by a decrease in the corrected count increment (CCI) on at least two occasions (1-hour CCI < 7500 or 24-hour CCI < 4500 post-transfusion). Daratumumab was administered intravenously at a dose of 8 mg per kilogram of body weight once weekly for four consecutive weeks. The primary endpoints were adverse events and overall response rate (ORR), defined as the percentage of patients achieving at least two effective platelet transfusions, followed by a 12-week follow-up.

Results

A total of 10 patients were recruited with 8 reaching the 12-week primary endpoint. Within this subset, one patient was administered daratumumab monotherapy, six received a combination therapy with cyclosporine, and one was treated with a regimen including tacrolimus and danazol. The median baseline platelet count was 2.5×10⁹ per liter (range, 1 to 13). The ORR at 12 weeks was 87.5% (7 out of 8 patients), with a median time to response of 3 weeks (range, 1 to 6). The most frequently observed adverse events were grade 1-2 electrolyte imbalances (75%) and grade 1 general symptoms (62.5%), such as fatigue, headache, and insomnia. Throughout the study, a total of 38 transfusions were administered, with transfusion reactions occurring in 4 cases (10.5%). The infection rate during the 12-week follow-up period was 50% (4 out of 8 participants), with infections classified as severity grade 2-3. Importantly, no fatalities were reported during the study period.

Conclusion

Anti-CD38 targeted therapy demonstrates promising preliminary efficacy in addressing platelet transfusion refractoriness, while exhibiting mild and tolerable adverse reactions in patients with aplastic anemia. (Funded by the National Clinical Research Center for Blood Diseases Fund for Clinical Research; ClinicalTrial.gov ID: NCT05832216).

Keywords: Aplastic anemia, Platelet transfusion refractoriness, CD38 monoclonal antibodies

No relevant conflicts of interest to declare.

Daratumumab is a monoclonal antibody employed in the therapeutic management of multiple myeloma, a malignancy characterized by the proliferation of abnormal plasma cells within the bone marrow. This agent exerts its effects by specifically targeting the CD38 protein, which is abundantly expressed on the surface of myeloma cells.