Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma

• Published in: Leukemia & lymphoma 2021-07, Vol.62 (9), p.2094-2106
• Main Authors: Wilson, Wyndham H., Phillips, Tycel, Popplewell, Leslie, de Vos, Sven, Chhabra, Saurabh, Kimball, Amy S., Beaupre, Darrin, Huang, Da Wei, Wright, George, Kwei, Kevin, Ping, Jerry, Neuenburg, Jutta K., Staudt, Louis M.
• Format: Article
• Language: English
• Subjects: activated B-cell-like; Adenine - analogs & derivatives; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; diffuse large B-cell lymphoma; dose-adjusted EPOCH-R; Doxorubicin; Etoposide; germinal center B-cell-like; Humans; Ibrutinib; Lenalidomide; Lymphoma, Large B-Cell, Diffuse - drug therapy; Piperidines; Prednisone; Treatment Outcome; Vincristine
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2021.1907371

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is difficult to cure; non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) DLBCL have worse outcomes than GCB DLBCL. Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy. In part 1 of this phase 1b/2 study (NCT02142049), patients with relapsed/refractory DLBCL received ibrutinib 560 mg and escalating doses of lenalidomide on Days 1-7 with DA-EPOCH-R (Days 1-5) in 21-day cycles. In part 1 (N = 15), the maximum tolerated dose was not reached with lenalidomide 25 mg (recommended part 2 dose [RP2D]); most common grade ≥3 adverse events were anemia (73%) and febrile neutropenia (47%); the overall response rate (ORR) was 40%. At the RP2D (n = 26), ORR was 71% in non-GCB and 64% in ABC. Ibrutinib and lenalidomide with DA-EPOCH-R had a manageable safety profile and antitumor activity in relapsed/refractory DLBCL, especially the non-GCB subtype.