Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

Abstract

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

• Authors: Robin Foà, Ilaria Del Giudice, Antonio Cuneo, Giovanni Del Poeta, Stefania Ciolli, Francesco Di Raimondo, Francesco Lauria, Emanuele Cencini, Gian Matteo Rigolin, Agostino Cortelezzi, Francesco Nobile, Vincenzo Callea, Maura Brugiatelli, Massimo Massaia, Stefano Molica, Livio Trentin, Rita Rizzi, Giorgina Specchia, Francesca Di Serio, Lorella Orsucci, Achille Ambrosetti, Marco Montillo, Pier Luigi Zinzani, Felicetto Ferrara, Fortunato Morabito, Maria Angela Mura, Silvia Soriani, Nadia Peragine, Simona Tavolaro, Silvia Bonina, Marilisa Marinelli, Maria Stefania De Propris, Irene Della Starza, Alfonso Piciocchi, Alessandra Alietti, Eva Josephine Runggaldier, Enrica Gamba, Francesca Romana Mauro, Sabina Chiaretti, Anna Guarini
• Journal: American journal of hematology (Am J Hematol) Vol. 89 Issue 5 Pg. 480-6 (May 2014) ISSN: 1096-8652 [Electronic] United States
• PMID: 24415640 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Chlorambucil
• Rituximab

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chlorambucil (administration & dosage)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Induction Chemotherapy
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Male
• Rituximab
• Survival Analysis
• Treatment Outcome