Researchers evaluated the addition of ibrutinib to fludarabine, cyclophosphamide, and obinutuzumab (iFCG) in previously untreated patients with IGHV-mutated chronic lymphocytic leukemia (CLL). Eligible patients were aged ≥18 years with no del(17p)/TP53 mutation or unmutated IGHV. Chemotherapy was limited to 3 courses, potentially reducing short- and long-term toxicity, while increasing efficacy through the addition of ibrutinib and obinutuzumab. Ibrutinib was given for 9 courses, and obinutuzumab was given for 3 courses if patients achieved complete remission (CR)/CR with incomplete marrow recovery (CRi) with bone marrow undetectable minimal residual disease (MRD) or 9 courses if patients had only achieved partial response and/or were bone marrow MRD–positive.
In the initial phase, the primary end point was CR/CRi. Patients achieving CR/CRi or partial response at 1 year stopped all therapy, including ibrutinib, whereas patients who were MRD-positive at 1 year were permitted to continue ibrutinib.
A total of 45 patients enrolled, and median follow-up was 22.3 months. With iFCG, all 44 evaluable patients achieved either complete (39%) or partial response (61%) at 3 months, and 89% had undetectable MRD in their bone marrow. Responses continued to improve over time. At 12 months, the CR/CRi rate was 86%, and all patients had undetectable MRD. All 32 remaining evaluable patients had undetectable MRD status at a median follow-up of 13.6 months and discontinued ibrutinib. No patient has progressed on treatment and all but 4 patients continue on study protocol.
Neutropenia was the most common hematologic grade 3/4 adverse event, occurring in 53% of patients during cycles 1 through 3, and 27% of patients during cycles 4 through 12. Atrial fibrillation (all grades) occurred in 11% of patients, and 1 fatality was reported in a patient with no cardiac history who developed congestive heart failure during cycle 9 of treatment.
Researchers concluded that iFCG achieved a high rate of undetectable MRD in previously untreated patients with IGHV-mutated CLL. Clearly, this therapeutic option holds promise as a first-line option and warrants further study.
Jain N, et al. ASH 2018. Abstract 185.