title: The efficacy of rituximab plus Hyper-CVAD regimen in mantle cell lymphoma is independent of FCgammaRIIIa and FCgammaRIIa polymorphisms.
abstract: Mantle cell lymphoma (MCL) accounts for 3-10% of all non-Hodgkin's lymphomas, with median overall survival not exceeding 3-4 years. Rituximab in combination with the Hyper-CVAD regimen appears the most promising regimen; thus, we adopted it as a first-line treatment strategy in a series of 24 patients. In addition to evaluation of clinical success of the regimen, we investigated a possible role of polymorphism in IgG Fc receptors, FCgammaRIIIa and FCgammaRIIa. The frequencies of FCgammaRIIIa-158 were as follows: V/V=4/24 (17%); V/F=16/24 (66%); F/F=4/24 (17%). Those of the FCgammaRIIa-131 polymorphism were H/H=11/24 (46%), H/R=9/24 (37%), R/R=4/24 (17%). The overall response rate was 62.5%, with 33% of complete responses (CRs) after four cycles of R-Hyper-CVAD. Two-year progression-free survival (PFS) was 78% for 158V/V patients vs 75% for cases carrying phenylalanine (p=0.88). When the FCgammaRIIa polymorphism was assessed, the 2-year PFS was 82% for 131H/H patients vs 75% for those carrying arginine (p=0.26). Eighty-three percent of cases achieved Polymerase Chain Reaction (PCR)-negativity: the progression rate was significantly influenced by the minimal residual disease clearance, with 12% progression in the subgroup of PCR-negative cases versus 67% progression in PCR-positive cases (p=0.008). The achievement of PCRnegativity was not significantly influenced by FCgammaR polymorphisms. Results confirm that rituximab plus Hyper-CVAD is an effective regimen for the induction of prolonged remission in patients with aggressive MCL and suggest that rituximab efficacy is independent of the FCgammaR polymorphisms.
authors.affiliation: Department of Oncology, Section of Hematology, University of Pisa, Pisa, Italy. s.galimberti@med.unipi.it
authors.forename: S
authors.initials: S
authors.lastname: Galimberti
authors.forename: G A
authors.initials: GA
authors.lastname: Palumbo
authors.forename: F
authors.initials: F
authors.lastname: Caracciolo
authors.forename: E
authors.initials: E
authors.lastname: Benedetti
authors.forename: M
authors.initials: M
authors.lastname: Pelosini
authors.forename: S
authors.initials: S
authors.lastname: Brizzi
authors.forename: E
authors.initials: E
authors.lastname: Ciabatti
authors.forename: R
authors.initials: R
authors.lastname: Fazzi
authors.forename: C
authors.initials: C
authors.lastname: Stelitano
authors.forename: G
authors.initials: G
authors.lastname: Quintana
authors.forename: E
authors.initials: E
authors.lastname: Conte
authors.forename: D
authors.initials: D
authors.lastname: Tibullo
authors.forename: F
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: M
authors.initials: M
authors.lastname: Petrini
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide