Favorable Long-term PFS in Patients with CLL, Mutated IGHV Following FCR Treatment

By Cailin Conner - Last Updated: September 25, 2023

Patients with chronic lymphocytic lymphoma (CLL) and mutated IGHV genes (IGHV-M) had favorable progression-free survival (PFS) over a long-term period after chemoimmunotherapy treatment with fludarabine, cyclophosphamide, and rituximab (FCR), according to an updated follow-up1 of a phase II study conducted at the University of Texas MD Anderson Cancer Center in 1999.2

Philip A. Thompson, from the Royal Melbourne Hospital in Australia, and colleagues published their research in Blood.

Expanding upon the original FCR phase II study, which evaluated 300 patients with CLL at a median follow-up of six years, investigators updated the long-term follow-up results after 19 years. The researchers compared the PFS of FCR treatment between patients with CLL and IGHV-M and those with unmutated IGHV (IGHV-UM).

Patients with IGHV-M experienced a median PFS of 14.6 years compared with 4.2 years in patients with IGHV-UM.

Moreover, disease progression was uncommon beyond 10 years. Of the 94 patients in remission after 10 years, 16 (17%) patients experienced disease progression. Among patients with IGHV-M, just four of 45 (9%) progressed beyond the 10-year milestone.

In addition to reporting on CLL remission and PFS, the investigators examined the incidence of secondary malignancies. Among the 300 patients with CLL, 96 (32%) developed 106 other malignancies; 19 patients (6.3%) developed therapy-related myeloid neoplasms, which were fatal in 84% of these patients. The investigators did not identify any pretreatment patient characteristics that could predict the risk of therapy-related myeloid neoplasms.

“In summary, FCR remains an option for patients with IGHV-M CLL, with a significant fraction achieving functional cure of CLL,” the investigators wrote. “A risk-benefit assessment is warranted when counseling patients, balancing potential functional cure with the risk of late relapses and serious secondary malignancies.”


  1. Thompson PA, Bazinet A, Wierda WG, et al. Sustained remissions in CLL after frontline FCR treatment with very long-term follow-up. Blood. 2023. doi:10.1182/blood.2023020158
  2. Tam CS, O’Brien S, Weirda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. 2008;112(4):975-980. doi:10.1182/blood-2008-02-140582
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