title: Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: a randomized phase II study from the Nordic Lymphoma Group.
abstract: The purpose of this phase II randomized trial was to evaluate the effect and safety of interferon-alpha2a (IFN) in combination with extended dosing rituximab in patients with symptomatic, advanced indolent lymphoma responding to a standard single course of rituximab. Totally 123 patients were treated with rituximab 375 mg/m2 once weekly for 4 weeks leading to 14 complete response (CR; 11%), 56 partial response (PR; 46%), and 13 minor responses (MR; 11%). Patients achieving either PR or MR were randomized to four more infusions of rituximab alone (n = 36) or in combination with five weeks of IFN (n = 33), with an overall response rate (CR + PR) of 78% and 94%, respectively. Significantly more patients in the combination arm improved their response from PR/MR to CR (P < 0.05) and more maintained their responses for > or = 24 months (72% versus 50%), respectively. Overall, 26 out of the 52 patients who achieved CR underwent minimal residual disease (MRD) evaluation. Totally 17 of these (65%) achieved MRD negativity, 14 of whom remain in CR after 4.8 years' follow-up. The addition of IFN to rituximab was generally safe, but reversible thrombocytopenia and neutropenia were noted in one and six patients, respectively, requiring a reduction in the IFN dose. Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden. eva@kimby.se
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.forename: Hans
authors.initials: H
authors.lastname: Hagberg
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Tuula
authors.initials: T
authors.lastname: Lehtinen
authors.forename: Björn
authors.initials: B
authors.lastname: Ostenstad
authors.forename: Mads
authors.initials: M
authors.lastname: Hansen
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Ola
authors.initials: O
authors.lastname: Lindén
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D009503:Neutropenia / Q000139:chemically induced; D011994:Recombinant Proteins; D012074:Remission Induction; D000069283:Rituximab; D013548:Sweden; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000069283:Rituximab