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.
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.


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.
Blum
K A
KA
Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH. Electronic address: kristie.blum@osumc.edu.
Jung
S-H
SH
CALGB Statistical Center, Duke University Medical Center, Durham, NC.
Johnson
J L
JL
CALGB Statistical Center, Duke University Medical Center, Durham, NC.
Lin
T S
TS
Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
Hsi
E D
ED
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH.
Lucas
D M
DM
Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
Byrd
J C
JC
Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
Cheson
B D
BD
Division of Hematology-Oncology, Georgetown University Hospital, Washington, DC.
Bartlett
N L
NL
Division of Hematology-Oncology, Washington University School of Medicine, St Louis, MO, USA.
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D000911:Antibodies, Monoclonal; C496124:FCGR3A protein, human; D017452:Receptors, IgG; C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D014747:Vinblastine; D004317:Doxorubicin; C504717:SGN-30 monoclonal antibody; D000077235:Vinorelbine; D000093542:Gemcitabine