A Multicenter Open-Label, Phase 1b/2 Study Of Ibrutinib In Combination With Lenalidomide And Rituximab In Patients With Relapsed Or Refractory (R/R) Diffuse Large B-Cell Lymphoma (Dlbcl)

Background: DLBCL is the most common subtype (30-40%) of non-Hodgkin lymphoma and 50-60% of patients (pts) are cured with standard R-CHOP therapy. Among pts who fail R-CHOP, only 10-20% experience prolonged disease-free intervals with high-dose chemotherapy and autologous stem cell transplant (SCT). In particular, pts relapsing within 12 months (mo) of diagnosis and/or refractory pts have a very poor outcome (Crump, ASCO 2016). In addition, many pts are SCT-ineligible due to advanced age and/or comorbidities (Friedberg, ASH Educ Program 2011). Therefore, R/R DLBCL represents a clear unmet medical need. Ibrutinib (ibr), a first-in-class, oral, once-daily inhibitor of Bruton's tyrosine kinase, has shown activity as a single agent in R/R DLBCL, particularly in the non-germinal center B-cell-like (non-GCB) subtype (Wilson, Nat Med 2015). Lenalidomide (LEN) is an immunomodulatory agent that has shown activity in combination with rituximab (RTX) in phase 2 studies of R/R DLBCL (Wang, Leukemia 2013). This multicenter, open-label, phase 1b/2 study is designed to evaluate the safety and efficacy of ibr in combination with LEN and RTX in pts with R/R DLBCL. Here, we report preliminary results of the phase 1b portion of the study.