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.

• Authors: Jennifer A Woyach, Amy S Ruppert, Nyla A Heerema, Bercedis L Peterson, John G Gribben, Vicki A Morrison, Kanti R Rai, Richard A Larson, John C Byrd
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 10 Pg. 1349-55 (Apr 01 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21321292 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Rituximab
• Vidarabine
• fludarabine

Topics

• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cytogenetic Analysis
• Disease-Free Survival
• Genes, Immunoglobulin Heavy Chain
• Humans
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, genetics, immunology, mortality)
• Leukemia, Myeloid, Acute (chemically induced)
• London
• Mutation
• Proportional Hazards Models
• Risk Assessment
• Risk Factors
• Rituximab
• Survival Rate
• Time Factors
• Treatment Outcome
• United States
• Vidarabine (administration & dosage, analogs & derivatives)