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

Overview

Journal Ann Oncol

Publisher Elsevier

Specialty Oncology

Date 2010 Apr 29

PMID 20423913

Citations 19

Authors

K A Blum

S-H Jung

J L Johnson

T S Lin

E D Hsi

D M Lucas

J C Byrd

B D Cheson

N L Bartlett

Affiliations

Soon will be listed here.

Abstract

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.

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References

Golocheikine A, Saini D, Ramachandran S, Trulock E, Patterson A, Mohanakumar T . Soluble CD30 levels as a diagnostic marker for bronchiolitis obliterans syndrome following human lung transplantation. Transpl Immunol. 2007; 18(3):260-3. PMC: 2170881. DOI: 10.1016/j.trim.2007.07.007. View

Miettinen M . CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin's and non-Hodgkin's lymphomas. Arch Pathol Lab Med. 1992; 116(11):1197-201. View

Cerveny C, Law C, McCormick R, Lenox J, Hamblett K, Westendorf L . Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics. Leukemia. 2005; 19(9):1648-55. DOI: 10.1038/sj.leu.2403884. View

Oflazoglu E, Stone I, Gordon K, Grewal I, van Rooijen N, Law C . Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30. Blood. 2007; 110(13):4370-2. DOI: 10.1182/blood-2007-06-097014. View

Roychowdhury D, Cassidy C, Peterson P, Arning M . A report on serious pulmonary toxicity associated with gemcitabine-based therapy. Invest New Drugs. 2002; 20(3):311-5. DOI: 10.1023/a:1016214032272. View

Hartl D, Griese M, Kappler M, Zissel G, Reinhardt D, Rebhan C . Pulmonary T(H)2 response in Pseudomonas aeruginosa-infected patients with cystic fibrosis. J Allergy Clin Immunol. 2006; 117(1):204-11. DOI: 10.1016/j.jaci.2005.09.023. View

Santoro A, Bredenfeld H, Devizzi L, Tesch H, Bonfante V, Viviani S . Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol. 2000; 18(13):2615-9. DOI: 10.1200/JCO.2000.18.13.2615. View

Amakawa R, Hakem A, Kundig T, Matsuyama T, Simard J, Timms E . Impaired negative selection of T cells in Hodgkin's disease antigen CD30-deficient mice. Cell. 1996; 84(4):551-62. DOI: 10.1016/s0092-8674(00)81031-4. View

Wahl A, Klussman K, Thompson J, Chen J, Francisco L, Risdon G . The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002; 62(13):3736-42. View

10.

Bartlett N, Younes A, Carabasi M, Forero A, Rosenblatt J, Leonard J . A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood. 2007; 111(4):1848-54. PMC: 2275000. DOI: 10.1182/blood-2007-07-099317. View

11.

Baker C, Chang L, Elsegood K, Bishop A, Gannon D, Narendran P . Activated T cell subsets in human type 1 diabetes: evidence for expansion of the DR+ CD30+ subpopulation in new-onset disease. Clin Exp Immunol. 2007; 147(3):472-82. PMC: 1810485. DOI: 10.1111/j.1365-2249.2006.03307.x. View

12.

Bredenfeld H, Franklin J, Nogova L, Josting A, Fries S, Mailander V . Severe pulmonary toxicity in patients with advanced-stage Hodgkin's disease treated with a modified bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine (BEACOPP) regimen is probably related to the.... J Clin Oncol. 2004; 22(12):2424-9. DOI: 10.1200/JCO.2004.09.114. View

13.

Papiris S, Kollintza A, Karatza M, Manali E, Sotiropoulou C, Milic-Emili J . CD8+ T lymphocytes in bronchoalveolar lavage in idiopathic pulmonary fibrosis. J Inflamm (Lond). 2007; 4:14. PMC: 1906752. DOI: 10.1186/1476-9255-4-14. View

14.

Heuck F, Ellermann J, Borchmann P, Rothe A, Hansen H, Engert A . Combination of the human anti-CD30 antibody 5F11 with cytostatic drugs enhances its antitumor activity against Hodgkin and anaplastic large cell lymphoma cell lines. J Immunother. 2004; 27(5):347-53. DOI: 10.1097/00002371-200409000-00003. View

15.

Gruss H, Dower S . Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood. 1995; 85(12):3378-404. View

16.

Weng W, Levy R . Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003; 21(21):3940-7. DOI: 10.1200/JCO.2003.05.013. View

17.

Watanabe M, Yamamoto N, Maruoka H, Matsuzuka F, Miyauchi A, Iwatani Y . Relation of CD30 molecules on T-cell subsets to the severity of autoimmune thyroid disease. Thyroid. 2003; 13(3):259-63. DOI: 10.1089/105072503321582051. View

18.

Boin F, De Fanis U, Bartlett S, Wigley F, Rosen A, Casolaro V . T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. Arthritis Rheum. 2008; 58(4):1165-74. PMC: 2662772. DOI: 10.1002/art.23406. View

19.

Agnarsson B, Kadin M . The immunophenotype of Reed-Sternberg cells. A study of 50 cases of Hodgkin's disease using fixed frozen tissues. Cancer. 1989; 63(11):2083-7. DOI: 10.1002/1097-0142(19890601)63:11<2083::aid-cncr2820631102>3.0.co;2-u. View

20.

Friedberg J, Neuberg D, Kim H, Miyata S, McCauley M, Fisher D . Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity. Cancer. 2003; 98(5):978-82. DOI: 10.1002/cncr.11582. View