A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

A SUMMARY Ibrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab for First-Line Treatment of IGHV-Mutated CLL and Without Del(17p)/Mutated TP53 An investigator-initiated phase 2 trial evaluated the combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab as first-line treatment in patients with IGHV-mutated CLL (Abstract 357). Patients with the TP53 mutation or del(17p) were excluded from enrollment. All patients initially received 3 cycles of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab. Patients with undetectable bone marrow MRD then received 3 courses of obinutuzumab plus ibrutinib, followed by 6 cycles of ibrutinib monotherapy. All other patients received 9 courses of obinutuzumab plus ibrutinib. Patients with detectable bone marrow MRD after 12 treatment cycles continued with ibrutinib monotherapy. After 3 cycles of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab, 87% of patients had undetectable MRD in the bone marrow. After a median follow-up of 34.2 months, 31 patients (69%) had a CR or incomplete CR, and 44 patients (98%) had undetectable MRD in the bone marrow. Among 41 patients with 1 year of follow-up, all had undetectable bone marrow MRD and discontinued ibrutinib monotherapy per protocol. No clinical relapses were observed. One patient had an MRD relapse. Toxicities were manageable.