Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101.

Abstract

PURPOSE:

To determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia.

PATIENTS AND METHODS:

Patients (n = 102) received fludarabine 25 mg/m(2) intravenously days 1 to 5 and rituximab 50 mg/m(2) day 1, 325 mg/m(2) day 3, and 375 mg/m(2) day 5 of cycle 1 and then 375 mg/m(2) day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks.

RESULTS:

Overall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab.

CONCLUSION:

Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.

• Authors: Thomas S Lin, Kathleen A Donohue, John C Byrd, Margaret S Lucas, Eva E Hoke, Elizabeth M Bengtson, Kanti R Rai, James N Atkins, Brian K Link, Richard A Larson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 29 Pg. 4500-6 (Oct 10 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20697069 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal, Murine-Derived
• Antibodies, Neoplasm
• Alemtuzumab
• Rituximab
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Alemtuzumab
• Anemia (chemically induced)
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal, Murine-Derived
• Antibodies, Neoplasm (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Humans
• Injections, Subcutaneous
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Male
• Middle Aged
• Nausea (chemically induced)
• Neoplasm, Residual (drug therapy)
• Remission Induction
• Rituximab
• Treatment Outcome
• Vidarabine (administration & dosage, adverse effects, analogs & derivatives)
• Young Adult