The long-term follow-up of the randomized E1912 study comparing the long-term effectiveness of ibrutinib-rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) therapy is presented by the researchers for a study. In addition, the tolerability of continuous ibrutinib is also described.
The E1912 study included 529 treatment-naive patients with chronic lymphocytic leukemia (CLL) aged ≤70 years. Patients were randomly randomized (2:1) to either IR or FCR for 6 cycles. The median progression-free survival (PFS) with a median follow-up of 5.8 years was superior for IR (hazard ratio [HR], 0.37; P<.001).
In patients with both immunoglobulin heavy chain variable region (IGHV) gene mutant and unmutated CLL, IR improved PFS compared to FCR (HR: 0.27; P<.001). Ibrutinib was continued in 214 (60.5%) of the 354 patients who were randomly assigned to IR. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of those who started IR) did so due to disease progression or death, 77 (21.9% of those who started IR) discontinued due to adverse events (AEs)/complications, and 24 (6.8% of those who started IR) did so for other reasons. Progression was infrequent in people who could continued to take ibrutinib. Among patients who stopped using ibrutinib for reasons other than its progression, the median period from withdrawal to disease progression or death was 25 months. Patients in the IR arm had a sustained improvement in overall survival (OS) (HR, 0.47; P=.018).
In conclusion, IR treatment provided improved PFS and OS compared to FCR in patients with IGHV mutant or unmutated CLL. In addition, the majority of CLL patients tolerated continuous ibrutinib treatment for more than 5 years.