Safety and efficacy of daratumumab in immune thrombocytopenia.

abstractResistance to B-cell-targeted therapies in immune thrombocytopenia (ITP) has been linked to persistence of autoantibody-producing CD38+ long-lived plasma cells. CD38 antibody daratumumab has been proposed as a potential therapy for ITP. This multicenter, open-label, phase 2 study evaluated safety and efficacy of daratumumab in 21 patients with previously treated ITP. Following a safety run-in, 2 dosing cohorts received 8 and 10 subcutaneous injections of 1800 mg daratumumab weekly, respectively. Primary end points were safety and response (2 consecutive platelet counts ≥50 × 109/L at week 12 for the safety run-in/cohort 1, and at week 16 for cohort 2). At baseline, median platelet count was 17 × 109/L, median number of prior therapies was 4. Most treatment-emergent adverse events were transient grade 1 to 2, most commonly infections (38%). Two patients (4.7%) experienced grade 3 adverse events, 1 infusion-related reaction, and 1 severe acute respiratory syndrome coronavirus 2 infection with acute renal failure. Ten patients (48%) met the primary efficacy end point. Sustained response (2 consecutive platelet counts ≥50 × 109/L at week 24) was achieved in 8 patients (38%), of whom 2 later relapsed. Response and relapse rates did not differ between cohorts. Patient-reported quality of life measured by 36-Item Short-Form Health Survey 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 antiplatelet antibodies between responders and nonresponders. This study confirms CD38 as an important target in ITP. This trial was registered at clinicaltrials.gov as #NCT04703621, and at the European Clinical Trial Register (EudraCT #2019-004683-22).