title: Attainment of complete/very good partial response following rituximab-based therapy is an important determinant to progression-free survival, and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia.
abstract: The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. The median follow-up was 33·5 months, and categorical responses were as follows: complete response (CR, 8·8%); very good partial response (VGPR, 13·2%); partial response (50%); minor response (18·9%); Non-Responders (8·8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0·0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time-to-progression. Neither age, serum IgM, haematocrit, platelet count, serum β(2) microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A-48 and -158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P ≤ 0·03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab-naïve WM patients undergoing rituximab-based therapy, and was predicted by polymorphisms in FCGR3A.
authors.affiliation: Bing Center for Waldenstrom's Macroglobulinaemia, Dana Farber Cancer Institute, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Christine
authors.initials: C
authors.lastname: Hanzis
authors.forename: Leukothea
authors.initials: L
authors.lastname: Ioakimidis
authors.forename: Sigitas J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fox
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Hsiuyi
authors.initials: H
authors.lastname: Tseng
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Manning
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheehy
authors.forename: Barry
authors.initials: B
authors.lastname: Turnbull
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000235:genetics
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab