Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712

Abstract

Purpose: The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited.

Methods: We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN).

Results: A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse.

Conclusion: Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram. FR, rituximab with fludarabine.

Fig 2.

Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) for all 104 patients on Cancer and Leukemia Group B study CALGB 9712.

Fig 3.

Kaplan-Meier estimates of overall survival after progression.

Fig 4.

(A) Kaplan-Meier estimates of progression-free survival (PFS) in patients with mutated immunoglobulin heavy chain variable region (IgVH) versus unmutated IgVH. (B) Kaplan-Meier estimates of overall survival (OS) in patients with mutated IgVH versus unmutated IgVH. (C) Kaplan-Meier estimates of PFS in patients with del(17p13.1)/del(11q22.3) versus those without these poor-risk abnormalities. (D) Kaplan-Meier estimates of OS in patients with del(17p13.1)/del(11q22.3) versus those without these poor-risk abnormalities.