Fludarabine, cyclophosphamide, and rituximab (FCR)-treated patients with immunoglobulin heavy chain variable (IGHV)-mutated chronic lymphocytic leukemia (CLL) achieve long-term disease-free survival, a new study published online ahead of print in the journal Blood has shown.1

Because patients with CLL now have less toxic alternatives like ibrutinib, it is essential to identify those most likely to achieve long-term disease-free survival after chemoimmunotherapy.

One such approach, FCR, has achieved a high initial response rate in a phase 2 study, but continued relapses were observed. Therefore, researchers sought to evaluate the impact of FCR on disease-free and progression-free survival in patients with CLL and a mutated IGHV gene.

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Results showed that at a median follow-up of 12.8 years, progression-free survival (PFS) was 30.9% in all patients with CLL, but 53.9% for patients with IGHV­-mutated CLL and 8.7% for those with unmutated IGHV. Researchers observed no relapses beyond 10.4 years in 42 patients.

The study also demonstrated that minimal residual disease (MRD)-negativity after treatment was highly predictive of long-term disease-free survival, especially in IGHV-mutated disease.

“The high rate of very long-term PFS in patients with IGHV-M after FCR argues for the continued use of chemoimmunotherapy in this patient subgroup outside of clinical trials. In contrast, alternative strategies may be preferred in patients with IGHV-UM, to limit long-term toxicity,” the authors concluded.


  1. Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide and rituximab achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia [published online ahead of print October 22, 2015]. Blood. doi: 10.1182/blood-2015-09-667675.