Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma

Arnold Freedman, Sattva S. Neelapu, Craig Nichols, Michael Robertson, Benjamin Djulbegovic, Jane N. Winter, John F. Bender, Daniel P. Gold, Richard G. Ghalie, Morgan E. Stewart, Vanessa Esquibel, Paul Hamlin

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Abstract

Purpose: To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma. Patients and Methods: Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization. Results: A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GMCSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions. Conclusion: TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.

Original languageEnglish
Pages (from-to)3036-3043
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number18
DOIs
StatePublished - Jun 20 2009
Externally publishedYes

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Follicular Lymphoma
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Placebos
Random Allocation
Therapeutics
Rituximab
Disease Progression
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. / Freedman, Arnold; Neelapu, Sattva S.; Nichols, Craig; Robertson, Michael; Djulbegovic, Benjamin; Winter, Jane N.; Bender, John F.; Gold, Daniel P.; Ghalie, Richard G.; Stewart, Morgan E.; Esquibel, Vanessa; Hamlin, Paul.

In: Journal of Clinical Oncology, Vol. 27, No. 18, 20.06.2009, p. 3036-3043.

Research output: Contribution to journalArticle

Freedman, Arnold ; Neelapu, Sattva S. ; Nichols, Craig ; Robertson, Michael ; Djulbegovic, Benjamin ; Winter, Jane N. ; Bender, John F. ; Gold, Daniel P. ; Ghalie, Richard G. ; Stewart, Morgan E. ; Esquibel, Vanessa ; Hamlin, Paul. / Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 18. pp. 3036-3043.
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abstract = "Purpose: To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma. Patients and Methods: Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization. Results: A total of 349 patients were randomly assigned; median age was 54 years, 79{\%} were treatment naive, and 86{\%} had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GMCSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76{\%} of adverse events were mild or moderate, and 94{\%} of patients had injection site reactions. Conclusion: TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.",
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AU - Freedman, Arnold

AU - Neelapu, Sattva S.

AU - Nichols, Craig

AU - Robertson, Michael

AU - Djulbegovic, Benjamin

AU - Winter, Jane N.

AU - Bender, John F.

AU - Gold, Daniel P.

AU - Ghalie, Richard G.

AU - Stewart, Morgan E.

AU - Esquibel, Vanessa

AU - Hamlin, Paul

PY - 2009/6/20

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N2 - Purpose: To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma. Patients and Methods: Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization. Results: A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GMCSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions. Conclusion: TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.

AB - Purpose: To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma. Patients and Methods: Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization. Results: A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GMCSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions. Conclusion: TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.

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