Rituximab, lenalidomide, and ibrutinib before chemotherapy for newly diagnosed large B-cell lymphoma

Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest that the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset. The phase 2 Smart Start trial at MD Anderson Cancer Center (Houston, TX) evaluated the combination of rituximab, lenalidomide, and ibrutinib (RLI) for two cycles before addition of standard chemotherapy to RLI for six additional cycles for newly diagnosed non-germinal center B-cell-like DLBCL. RLI induced a high ORR, and RLI with chemotherapy resulted in durable responses. The progression-free and overall survival rates werd 91.3% and 96.6% at 2 years, respectively. The authors conclude that Smart Start establishes the potential for developing biologically drive and noncytotoxic first-line therapies for DLBCL.