Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression

Eric D Jacobsen, Jeff P Sharman, Yasuhiro Oki, Ranjana H Advani, Jane N Winter, Celeste M Bello, Gary Spitzer, Maria Corinna Palanca-Wessels, Dana A Kennedy, Pamela Levine, Jing Yang, Nancy L Bartlett

Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30-positive NHL. This planned subset analysis of B-cell NHLs includes 49 DLBCL patients and 19 with other B-cell NHLs. Objective response rate (ORR) was 44% for DLBCL, including 8 (17%) complete remissions (CR) with a median duration of 16.6 months thus far (range, 2.7 - 22.7+). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to frontline (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CR). Patients with other B-cell lymphomas also responded: 1 CR, 2 PRs of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with post-transplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. Combining brentuximab vedotin with rituximab was generally well tolerated with similar activity. Overall, significant activity with brentuximab vedotin was observed in refractory DLBCL and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov, NCT01421667.