title: 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.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Stefania
authors.initials: S
authors.lastname: Ciolli
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Francesco
authors.initials: F
authors.lastname: Lauria
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cencini
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Nobile
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Maura
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Massaia
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
authors.forename: Rita
authors.initials: R
authors.lastname: Rizzi
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Serio
authors.forename: Lorella
authors.initials: L
authors.lastname: Orsucci
authors.forename: Achille
authors.initials: A
authors.lastname: Ambrosetti
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Mura
authors.forename: Silvia
authors.initials: S
authors.lastname: Soriani
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonina
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Irene Della
authors.initials: ID
authors.lastname: Starza
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Alietti
authors.forename: Eva Josephine
authors.initials: EJ
authors.lastname: Runggaldier
authors.forename: Enrica
authors.initials: E
authors.lastname: Gamba
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D002699:Chlorambucil; D000069283:Rituximab