A phase 2a, single‐arm, open‐label study of tafasitamab, a humanized, Fc‐modified, anti‐CD19 antibody, in patients with relapsed/refractory B‐precursor cell acute lymphoblastic leukemia

BACKGROUND: B‐precursor cell acute lymphoblastic leukemia (B‐ALL) in adults is an aggressive and challenging condition, and patients with relapsed/refractory (R/R) disease after allogeneic stem cell transplantation (SCT), or noncandidates for SCT, have a particularly poor prognosis. The authors investigated the activity of the Fc‐modified anti‐CD19 antibody tafasitamab in adults with R/R B‐ALL (NCT01685021). METHODS: Adults with R/R B‐ALL received single‐agent tafasitamab 12 mg/kg weekly for up to four 28‐day cycles. Patients with complete remission (with or without neutrophil/platelet recovery; complete remission [CR] or complete remission with incomplete count recovery [CRi]) after cycles 2, 3, or 4 could continue tafasitamab every 2 weeks for up to 3 further months. The primary end point was overall response rate (ORR). RESULTS: Twenty‐two patients were treated (median, 2 prior lines of therapy; range, 1‐8). Six patients completed 2 cycles, and 2 of these patients responded for an ORR of 9%; 16 patients (73%) progressed before their first response assessment. Responses lasted 8 and 4 weeks in the 2 patients with CR and minimal residual disease (MRD)–negative CRi, respectively. Tafasitamab produced rapid B‐cell/blast depletion in 21 of 22 patients within 1 to 2 weeks of first administration. Tafasitamab was well tolerated, with the most frequent adverse events being infusion‐related reactions (59.1%) and fatigue (40.9%). Grade 3 to 4 febrile neutropenia (22.7%) was the most common hematologic adverse event. CONCLUSIONS: Tafasitamab monotherapy was associated with clinical activity in a subset of patients with R/R B‐ALL, including short‐lasting CR and MRD‐negative CRi. Given its favorable tolerability profile, further development of tafasitamab in chemoimmunotherapy combinations and MRD settings should be explored.