Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism.

Published

Journal Article

BACKGROUND:Based on in vitro synergistic cytotoxicity when anti-CD30 antibodies are combined with gemcitabine, the Cancer and Leukemia Group B conducted a double-blind, randomized, phase II trial of SGN-30 with gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) in patients with relapsed Hodgkin's lymphoma. PATIENTS AND METHODS:In part 1 of the trial, 16 patients received SGN-30 with GVD to assess the safety of the combination. In part 2, patients were randomly allocated to SGN-30 (n = 7) or placebo (n = 7) with GVD to determine overall response rate (ORR). RESULTS:ORR in all 30 patients was 63% (65% with SGN-30 plus GVD, n = 23, and 57% with placebo plus GVD, n = 7). Median event-free survival was 9.0 months, with no difference between the two arms. Grades 3-5 pneumonitis occurred in five patients receiving SGN-30 and GVD, leading to premature closure of the trial. All five patients with pulmonary toxicity had a V/F polymorphism in the FcγRIIIa gene (P = 0.008). CONCLUSIONS:Together with historical data demonstrating a 2% incidence of pulmonary events with GVD, these results indicate that SGN-30 cannot safely be administered concurrently. The risk of pneumonitis with SGN-30 and GVD is greatest in patients with an FcγRIIIa V/F polymorphism.

Full Text

Duke Authors

Cited Authors

  • Blum, KA; Jung, S-H; Johnson, JL; Lin, TS; Hsi, ED; Lucas, DM; Byrd, JC; Cheson, BD; Bartlett, NL; Cancer and Leukemia Group B,

Published Date

  • November 2010

Published In

Volume / Issue

  • 21 / 11

Start / End Page

  • 2246 - 2254

PubMed ID

  • 20423913

Pubmed Central ID

  • 20423913

Electronic International Standard Serial Number (EISSN)

  • 1569-8041

International Standard Serial Number (ISSN)

  • 0923-7534

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdq211

Language

  • eng