Daratumumab for quick and sustained remission in post-transplant relapsed/refractory acute lymphoblastic leukemia

Abstract B cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a heterogeneous disease that originates from immature B cells characterized by abnormal proliferation of lymphoid precursor cells in the bone marrow, peripheral blood and extramedullary sites [ 1 ]. It is a very common curable malignancy in children [ 2 ]. However, the overall survival of adult ALL has been limited to 30-40%. Although multi-drug combined chemotherapy can achieve complete remission (CR) in more than 80% of newly diagnosed adult patients with ALL, more than 50% of patients eventually relapse [ 3 ]. One of the reliable curative option is to achieve CR with subsequent allogenic hematopoietic stem cell transplantation (HSCT). However, relapse remains the major cause of failure of HSCT in patients with high-risk ALL. The therapeutic options in post-transplant relapsed/refractory ALL are limited. The outcome is poor with less than 10% of patients surviving five years [ 3 ]. Therefore, there is an urgent need for new treatment options. Daratumumab is a newly developed humanized monoclonal antibody targeting CD38 that has been approved for the treatment of refractory multiple myeloma. Remarkably, CD38 is also widely expressed on leukemia cells [ 4 ]. Here, we report an adult patient with ALL who relapsed post allogeneic HSCT and was resistant to treatment with DLI and anti-CD19/CD22 CAR-T cells. He was salvaged with a single dose treatment of daratumumab and achieved flow-based measurable residual disease (MRD) negativity (