Safety and Efficacy of Daratumumab in Immune Thrombocytopenia Open Access

• Treatment resistance in ITP has been linked to autoantibody- producing long-lived plasma cells, emphasizing the role of CD38 depletion.

• CD38 antibody daratumumab demonstrated short- and long-term efficacy with an acceptable safety profile in ITP patients.

Resistance to B-cell targeted therapies in immune thrombocytopenia (ITP) has been linked to persistence of autoantibody-producing CD38-positive long-lived plasma cells. CD38 antibody daratumumab has been proposed as a potential therapy for ITP. This multicenter, open-label, phase II study evaluated safety and efficacy of daratumumab in 21 previously treated ITP patients. Following a safety run-in, two dosing cohorts were included, receiving eight and ten subcutaneous injections of 1800 mg daratumumab weekly, respectively. Primary endpoints were safety and response (two consecutive platelet counts ≥50x109/L at week 12 for the safety run-in/Cohort 1, and at week 16 for Cohort 2). At baseline, median platelet count was 17x109/L, median number of prior therapies was four. Most treatment-emergent adverse events were transient grade 1-2, most commonly infections (38%).Two patients (4.7%) experienced grade 3 adverse events, one infusion-related reaction, and one SARS-CoV-2 infection with acute renal failure. Ten patients (48%) met the primary efficacy endpoint. Sustained response (two consecutive platelet counts ≥50x109/L at week 24) was achieved in eight patients (38%). Two patients relapsed after week 24. There was no difference in response or relapse rates between cohorts. Patient-reported quality of life measured by SF-36 improved in responding patients. Daratumumab decreased immunoglobulin levels in all patients, and substantially reduced CD38+ cells in peripheral blood and bone marrow. There was no significant difference in anti-platelet antibodies between responders and non-responders. This study confirms CD38 as an important target in ITP. NCT04703621; EudraCT 2019-004683-22.