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Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with Rituximab

Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with Rituximab
Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with Rituximab
PURPOSEInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODSA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles.ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSIONR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.
1527-7755
Fayad, Luis
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Offner, Fritz
e1a84c92-50cf-4647-a656-a89e0224b20e
Smith, Mitchell R.
a2d5eeeb-db4d-470d-893d-a08cb40d6993
Verhoef, Gregor
d9a1c9db-dbc6-45b1-b94d-64478dde3bfd
Johnson, Peter
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Kaufman, Jonathan L.
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Rohatiner, Ama
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Advani, Anjali
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Foran, James
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Hess, Georg
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Coiffier, Bertrand
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Czuczman, Myron
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Giné, Eva
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Durrant, Simon
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Kneissl, Michelle
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Luu, Kenneth T.
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Hua, Steven Y.
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Boni, Joseph
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Vandendries, Erik
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Dang, Nam H.
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Fayad, Luis
50beb380-411b-4342-92b9-dbc96321434e
Offner, Fritz
e1a84c92-50cf-4647-a656-a89e0224b20e
Smith, Mitchell R.
a2d5eeeb-db4d-470d-893d-a08cb40d6993
Verhoef, Gregor
d9a1c9db-dbc6-45b1-b94d-64478dde3bfd
Johnson, Peter
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Kaufman, Jonathan L.
692c2e1b-81f2-4a1d-8479-f8bf99cd6afd
Rohatiner, Ama
a8294ba6-84f3-4777-a499-c4e71ddf4a98
Advani, Anjali
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Foran, James
2a56e660-09c7-466b-9140-67bb5afb69f8
Hess, Georg
622c2070-a821-4447-b51b-cfdafc829884
Coiffier, Bertrand
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Czuczman, Myron
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Giné, Eva
9654b98f-afbc-4e8c-b0e0-5a7be5c86776
Durrant, Simon
a45244ba-1711-4984-b9ec-d3c45b080b44
Kneissl, Michelle
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Luu, Kenneth T.
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Hua, Steven Y.
5830d504-b00e-47a5-9965-0efd8cc06f90
Boni, Joseph
6007476b-2e19-479d-9bf3-0f572d44381a
Vandendries, Erik
c3b72fdd-8e0d-49ce-9d30-8bc17b08ae28
Dang, Nam H.
0320c463-d26c-4317-a1de-e26f5d3599cc

Fayad, Luis, Offner, Fritz, Smith, Mitchell R., Verhoef, Gregor, Johnson, Peter, Kaufman, Jonathan L., Rohatiner, Ama, Advani, Anjali, Foran, James, Hess, Georg, Coiffier, Bertrand, Czuczman, Myron, Giné, Eva, Durrant, Simon, Kneissl, Michelle, Luu, Kenneth T., Hua, Steven Y., Boni, Joseph, Vandendries, Erik and Dang, Nam H. (2013) Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with Rituximab. Journal of Clinical Oncology. (doi:10.1200/JCO.2012.42.7211). (PMID:23295790)

Record type: Article

Abstract

PURPOSEInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODSA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles.ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSIONR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.

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e-pub ahead of print date: 7 January 2013
Organisations: Cancer Sciences

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Local EPrints ID: 347151
URI: http://eprints.soton.ac.uk/id/eprint/347151
ISSN: 1527-7755
PURE UUID: 5c5d98e5-897b-43ac-b80b-a95d56d5c1d5
ORCID for Peter Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 18 Jan 2013 10:06
Last modified: 15 Mar 2024 02:58

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Contributors

Author: Luis Fayad
Author: Fritz Offner
Author: Mitchell R. Smith
Author: Gregor Verhoef
Author: Peter Johnson ORCID iD
Author: Jonathan L. Kaufman
Author: Ama Rohatiner
Author: Anjali Advani
Author: James Foran
Author: Georg Hess
Author: Bertrand Coiffier
Author: Myron Czuczman
Author: Eva Giné
Author: Simon Durrant
Author: Michelle Kneissl
Author: Kenneth T. Luu
Author: Steven Y. Hua
Author: Joseph Boni
Author: Erik Vandendries
Author: Nam H. Dang

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