Chemoimmunotherapy With Fludarabine and Rituximab Produces Extended Overall Survival and Progression-Free Survival in Chronic Lymphocytic Leukemia

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BlankChemoimmunotherapy With Fludarabine and Rituximab Produces Extended Overall

Survival and Progression-Free Survival in Chronic Lymphocytic Leukemia:

Long-Term Follow-Up of CALGB Study 9712

1.. A. Woyach,

2.. Amy S. Ruppert,

3.. Nyla A. Heerema,

4.. Bercedis L. ,

5.. G. Gribben,

6.. Vicki A. on,

7.. Kanti R. Rai,

8.. A. Larson and

9.. C. Byrd

+ Author Affiliations

1.. From Ohio State University, Columbus, OH; Duke University, Durham, NC;

Queen University of London, England; University of Minnesota; and Veterans

Affairs Medical Center Minneapolis, MN; North Shore-Long Island Jewish Medical

System, New Hyde Park, NY; and University of Chicago, IL.

1.. Corresponding author: C. Byrd, MD, B302 Starling Loving Hall, The

Ohio State University, 320 West 10th Ave, Columbus, OH 43210; e-mail:

.Byrd@....

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.