Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma

Stephen J. Schuster, Sattva S. Neelapu, Barry L. Gause, John Edward Janik, Franco M. Muggia, Jon P. Gockerman, Jane N. Winter, Christopher R. Flowers, Daniel A. Nikcevich, Eduardo M. Sotomayor, Dean S. McGaughey, Elaine S. Jaffe, Elise A. Chong, Craig W. Reynolds, Donald A. Berry, Carlos F. Santos, Mihaela A. Popa, Amy M. McCord, Larry W. Kwak

Research output: Contribution to journalArticle

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Abstract

Purpose: Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods: Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results: Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion: Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.

Original languageEnglish (US)
Pages (from-to)2787-2794
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number20
DOIs
StatePublished - Jul 10 2011

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Follicular Lymphoma
Neoplasm Antigens
Disease-Free Survival
Vaccination
Vaccines
Granulocyte Colony-Stimulating Factor
Monocytes
Hybridomas
Drug Therapy
Immunoglobulin Idiotypes
Safety Management
Random Allocation
Immunoglobulin M
Immunoglobulin G

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schuster, S. J., Neelapu, S. S., Gause, B. L., Janik, J. E., Muggia, F. M., Gockerman, J. P., ... Kwak, L. W. (2011). Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. Journal of Clinical Oncology, 29(20), 2787-2794. https://doi.org/10.1200/JCO.2010.33.3005

Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. / Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John Edward; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.

In: Journal of Clinical Oncology, Vol. 29, No. 20, 10.07.2011, p. 2787-2794.

Research output: Contribution to journalArticle

Schuster, SJ, Neelapu, SS, Gause, BL, Janik, JE, Muggia, FM, Gockerman, JP, Winter, JN, Flowers, CR, Nikcevich, DA, Sotomayor, EM, McGaughey, DS, Jaffe, ES, Chong, EA, Reynolds, CW, Berry, DA, Santos, CF, Popa, MA, McCord, AM & Kwak, LW 2011, 'Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma', Journal of Clinical Oncology, vol. 29, no. 20, pp. 2787-2794. https://doi.org/10.1200/JCO.2010.33.3005
Schuster, Stephen J. ; Neelapu, Sattva S. ; Gause, Barry L. ; Janik, John Edward ; Muggia, Franco M. ; Gockerman, Jon P. ; Winter, Jane N. ; Flowers, Christopher R. ; Nikcevich, Daniel A. ; Sotomayor, Eduardo M. ; McGaughey, Dean S. ; Jaffe, Elaine S. ; Chong, Elise A. ; Reynolds, Craig W. ; Berry, Donald A. ; Santos, Carlos F. ; Popa, Mihaela A. ; McCord, Amy M. ; Kwak, Larry W. / Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 20. pp. 2787-2794.
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abstract = "Purpose: Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods: Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results: Of 234 patients enrolled, 177 (81{\%}) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95{\%} CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95{\%} CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion: Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.",
author = "Schuster, {Stephen J.} and Neelapu, {Sattva S.} and Gause, {Barry L.} and Janik, {John Edward} and Muggia, {Franco M.} and Gockerman, {Jon P.} and Winter, {Jane N.} and Flowers, {Christopher R.} and Nikcevich, {Daniel A.} and Sotomayor, {Eduardo M.} and McGaughey, {Dean S.} and Jaffe, {Elaine S.} and Chong, {Elise A.} and Reynolds, {Craig W.} and Berry, {Donald A.} and Santos, {Carlos F.} and Popa, {Mihaela A.} and McCord, {Amy M.} and Kwak, {Larry W.}",
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TY - JOUR

T1 - Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma

AU - Schuster, Stephen J.

AU - Neelapu, Sattva S.

AU - Gause, Barry L.

AU - Janik, John Edward

AU - Muggia, Franco M.

AU - Gockerman, Jon P.

AU - Winter, Jane N.

AU - Flowers, Christopher R.

AU - Nikcevich, Daniel A.

AU - Sotomayor, Eduardo M.

AU - McGaughey, Dean S.

AU - Jaffe, Elaine S.

AU - Chong, Elise A.

AU - Reynolds, Craig W.

AU - Berry, Donald A.

AU - Santos, Carlos F.

AU - Popa, Mihaela A.

AU - McCord, Amy M.

AU - Kwak, Larry W.

PY - 2011/7/10

Y1 - 2011/7/10

N2 - Purpose: Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods: Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results: Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion: Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.

AB - Purpose: Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods: Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results: Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion: Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.

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