Active idiotypic vaccination versus control immunotherapy for follicular lymphoma

Ronald Levy, Kristen N. Ganjoo, John P. Leonard, Julie Marie Vose, Ian W. Flinn, Richard F. Ambinder, Joseph M. Connors, Neil L. Berinstein, Andrew R. Belch, Nancy L. Bartlett, Craig Nichols, Christos E. Emmanouilides, John M. Timmerman, Stephanie A. Gregory, Brian K. Link, David J. Inwards, Arnold S. Freedman, Jeffrey V. Matous, Michael J. Robertson, Lori A. Kunkel & 6 others Diane E. Ingolia, Andrew J. Gentles, Chih Long Liu, Robert Tibshirani, Ash A. Alizadeh, Dan W. Denney

Research output: Contribution to journalArticle

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Abstract

Purpose: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods: Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results: At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion: This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.

Original languageEnglish (US)
Pages (from-to)1797-1803
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number17
DOIs
StatePublished - Jun 10 2014

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Follicular Lymphoma
Immunotherapy
Vaccination
Disease-Free Survival
Granulocyte-Macrophage Colony-Stimulating Factor
Active Immunotherapy
Passive Immunization
Vincristine
Humoral Immunity
Prednisone
Cyclophosphamide
Reaction Time
Multicenter Studies
Antibody Formation
Immunoglobulins
Anti-Idiotypic Antibodies
Immunization
Lymphoma
Therapeutics
Vaccines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Levy, R., Ganjoo, K. N., Leonard, J. P., Vose, J. M., Flinn, I. W., Ambinder, R. F., ... Denney, D. W. (2014). Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. Journal of Clinical Oncology, 32(17), 1797-1803. https://doi.org/10.1200/JCO.2012.43.9273

Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. / Levy, Ronald; Ganjoo, Kristen N.; Leonard, John P.; Vose, Julie Marie; Flinn, Ian W.; Ambinder, Richard F.; Connors, Joseph M.; Berinstein, Neil L.; Belch, Andrew R.; Bartlett, Nancy L.; Nichols, Craig; Emmanouilides, Christos E.; Timmerman, John M.; Gregory, Stephanie A.; Link, Brian K.; Inwards, David J.; Freedman, Arnold S.; Matous, Jeffrey V.; Robertson, Michael J.; Kunkel, Lori A.; Ingolia, Diane E.; Gentles, Andrew J.; Liu, Chih Long; Tibshirani, Robert; Alizadeh, Ash A.; Denney, Dan W.

In: Journal of Clinical Oncology, Vol. 32, No. 17, 10.06.2014, p. 1797-1803.

Research output: Contribution to journalArticle

Levy, R, Ganjoo, KN, Leonard, JP, Vose, JM, Flinn, IW, Ambinder, RF, Connors, JM, Berinstein, NL, Belch, AR, Bartlett, NL, Nichols, C, Emmanouilides, CE, Timmerman, JM, Gregory, SA, Link, BK, Inwards, DJ, Freedman, AS, Matous, JV, Robertson, MJ, Kunkel, LA, Ingolia, DE, Gentles, AJ, Liu, CL, Tibshirani, R, Alizadeh, AA & Denney, DW 2014, 'Active idiotypic vaccination versus control immunotherapy for follicular lymphoma', Journal of Clinical Oncology, vol. 32, no. 17, pp. 1797-1803. https://doi.org/10.1200/JCO.2012.43.9273
Levy, Ronald ; Ganjoo, Kristen N. ; Leonard, John P. ; Vose, Julie Marie ; Flinn, Ian W. ; Ambinder, Richard F. ; Connors, Joseph M. ; Berinstein, Neil L. ; Belch, Andrew R. ; Bartlett, Nancy L. ; Nichols, Craig ; Emmanouilides, Christos E. ; Timmerman, John M. ; Gregory, Stephanie A. ; Link, Brian K. ; Inwards, David J. ; Freedman, Arnold S. ; Matous, Jeffrey V. ; Robertson, Michael J. ; Kunkel, Lori A. ; Ingolia, Diane E. ; Gentles, Andrew J. ; Liu, Chih Long ; Tibshirani, Robert ; Alizadeh, Ash A. ; Denney, Dan W. / Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 17. pp. 1797-1803.
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abstract = "Purpose: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods: Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44{\%}]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results: At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41{\%} of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion: This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.",
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T1 - Active idiotypic vaccination versus control immunotherapy for follicular lymphoma

AU - Levy, Ronald

AU - Ganjoo, Kristen N.

AU - Leonard, John P.

AU - Vose, Julie Marie

AU - Flinn, Ian W.

AU - Ambinder, Richard F.

AU - Connors, Joseph M.

AU - Berinstein, Neil L.

AU - Belch, Andrew R.

AU - Bartlett, Nancy L.

AU - Nichols, Craig

AU - Emmanouilides, Christos E.

AU - Timmerman, John M.

AU - Gregory, Stephanie A.

AU - Link, Brian K.

AU - Inwards, David J.

AU - Freedman, Arnold S.

AU - Matous, Jeffrey V.

AU - Robertson, Michael J.

AU - Kunkel, Lori A.

AU - Ingolia, Diane E.

AU - Gentles, Andrew J.

AU - Liu, Chih Long

AU - Tibshirani, Robert

AU - Alizadeh, Ash A.

AU - Denney, Dan W.

PY - 2014/6/10

Y1 - 2014/6/10

N2 - Purpose: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods: Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results: At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion: This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.

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