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

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

Research output: Contribution to journalArticle

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Abstract

Purpose Inotuzumab 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 Methods A 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. Results In 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/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). 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. Conclusion R-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.

Original languageEnglish (US)
Pages (from-to)573-583
Number of pages11
JournalJournal of Clinical Oncology
Volume31
Issue number5
DOIs
StatePublished - Feb 10 2013
Externally publishedYes

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Immunoconjugates
Non-Hodgkin's Lymphoma
Safety
Maximum Tolerated Dose
Antibodies
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Therapeutics
B-Cell Lymphoma
Disease-Free Survival
Inotuzumab Ozogamicin
Rituximab
Antibodies, Monoclonal, Humanized
Hyperbilirubinemia
Cytotoxins
Neutropenia
Thrombocytopenia
Anti-Idiotypic Antibodies
Survival Rate
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Journal of Clinical Oncology, Vol. 31, No. 5, 10.02.2013, p. 573-583.

Research output: Contribution to journalArticle

Fayad, L, Offner, F, Smith, MR, Verhoef, G, Johnson, P, Kaufman, JL, Rohatiner, A, Advani, A, Foran, JM, Hess, G, Coiffier, B, Czuczman, M, Giné, E, Durrant, S, Kneissl, M, Luu, KT, Hua, SY, Boni, J, Vandendries, E & Dang, NH 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, vol. 31, no. 5, pp. 573-583. https://doi.org/10.1200/JCO.2012.42.7211
Fayad, Luis ; Offner, Fritz ; Smith, Mitchell R. ; Verhoef, Gregor ; Johnson, Peter ; Kaufman, Jonathan L. ; Rohatiner, Ama ; Advani, Anjali ; Foran, James M ; Hess, Georg ; Coiffier, Bertrand ; Czuczman, Myron ; Giné, Eva ; Durrant, Simon ; Kneissl, Michelle ; Luu, Kenneth T. ; Hua, Steven Y. ; Boni, Joseph ; Vandendries, Erik ; Dang, Nam H. / 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. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 5. pp. 573-583.
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abstract = "Purpose Inotuzumab 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 Methods A 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. Results In 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/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). 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. Conclusion R-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.",
author = "Luis Fayad and Fritz Offner and Smith, {Mitchell R.} and Gregor Verhoef and Peter Johnson and Kaufman, {Jonathan L.} and Ama Rohatiner and Anjali Advani and Foran, {James M} and Georg Hess and Bertrand Coiffier and Myron Czuczman and Eva Gin{\'e} and Simon Durrant and Michelle Kneissl and Luu, {Kenneth T.} and Hua, {Steven Y.} and Joseph Boni and Erik Vandendries and Dang, {Nam H.}",
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T1 - Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-hodgkin lymphoma

T2 - Results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab

AU - Fayad, Luis

AU - Offner, Fritz

AU - Smith, Mitchell R.

AU - Verhoef, Gregor

AU - Johnson, Peter

AU - Kaufman, Jonathan L.

AU - Rohatiner, Ama

AU - Advani, Anjali

AU - Foran, James M

AU - Hess, Georg

AU - Coiffier, Bertrand

AU - Czuczman, Myron

AU - Giné, Eva

AU - Durrant, Simon

AU - Kneissl, Michelle

AU - Luu, Kenneth T.

AU - Hua, Steven Y.

AU - Boni, Joseph

AU - Vandendries, Erik

AU - Dang, Nam H.

PY - 2013/2/10

Y1 - 2013/2/10

N2 - Purpose Inotuzumab 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 Methods A 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. Results In 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/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). 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. Conclusion R-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.

AB - Purpose Inotuzumab 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 Methods A 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. Results In 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/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). 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. Conclusion R-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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