Ibrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (iFCG) for First-Line Treatment of Patients with CLL with Mutated IGHV

Conference Correspondent —December 17, 2018


ASH 2018

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.

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Last modified: December 17, 2018

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