Ibrutinib added to standard conditioning and as maintenance therapy following autologous hematopoietic stem cell transplantation for relapsed or refractory activated-B-cell type Diffuse Large B-cell lymphoma: primary analysis of the US intergroup double-blind randomized phase III study Alliance A051301/BMT-CTN 1201.

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (p = 0.09). We observed a higher incidence of grade ≥3 sepsis (10% vs 5%) and mucositis (13% vs. 3%) on ibrutinib but similar rates of atrial fibrillation. There were 4 fatalad verse events in the ibrutinib arm due to infection. Ibrutinib added to transplant may improve 2yPFS in relapsed/refractory ABC-DLBCL but future clinical trials should incorporate more efficient patient selection.