Long-term follow-up of ibrutinib plus rituximab (IR) treatment of chronic lymphocytic leukemia (CLL) demonstrated that the regimen is well tolerated by most patients and resulted in sustained improvement in survival, according to an analysis of the E1912 phase 3 trial published in Blood.

The initial analysis of the E1912 trial demonstrated that IR significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with fludarabine plus cyclophosphamide and rituximab (FCR) among patients with CLL. This analysis includes data from a median of 5.8 years of follow-up, which was 3 additional years from the initial report.

The E1912 trial randomly assigned 529 treatment-naïve patients with CLL 2:1 to receive IR until disease progression or unacceptable toxicity, or 6 cycles of FCR. The primary endpoint was PFS and secondary endpoints included OS.

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In this long-term follow-up, a modestly longer OS was sustained in the IR arm compared with the FCR arm, with 5-year OS rates of 95% and 89%, respectively (hazard ratio [HR], 0.47; 95% CI, 0.25-0.89; P =.018).

PFS also remained significantly longer in the IR group, with a 5-year PFS of 78% with IR compared with 51% with FCR (HR 0.37; 95% CI, 0.27-0.51; P <.0001). This benefit was observed regardless of the presence of IGHV mutation, with 5-year rates of 83% or 68% with IR or FCR, respectively (HR, 0.27; 95% CI, 0.11-0.62; P =.001) or 75% and 33%, respectively, with no mutation (HR, 0.27; 95% CI, 0.18-0.41 P <.0001).

There were 10.5% of patients who discontinued ibrutinib due to disease progression or death and 21.9% who discontinued due to adverse events (AEs) or complications. Study withdrawal for other reasons occurred for 6.8% of patients. The rate of grade 3 or higher AEs occurred less frequently in the IR arm compared with the FCR arm. The development of a secondary cancer occurred among 15.6% of patients who received IR compared with 10.8% of patients who received FCR.

“In conclusion,” the authors wrote, “with a median follow-up of approximately 6 years, the long-term results of the E1912 trial continue to demonstrate superior PFS and OS for IR therapy relative to FCR in patients with mutated or unmutated IGHV.”

Disclosures: This study was supported in part by Pharmacyclics, Inc (a subsidiary of AbbVie). Please see the original reference for a full list of disclosures.


Shanafelt TD, Want XV, Hanson CA, et al. Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial. Blood. 2022;140:112-120. doi: 10.1182/blood.2021014960