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

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.

• Authors: Stephen J Schuster, Sattva S Neelapu, Barry L Gause, John E 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 20 Pg. 2787-94 (Jul 10 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21632504 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Immunoglobulin Idiotypes

Topics

• Cancer Vaccines (adverse effects, immunology, therapeutic use)
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Immunoglobulin Idiotypes (adverse effects, immunology, therapeutic use)
• Lymphoma, Follicular (immunology, pathology, therapy)
• Male
• Middle Aged
• Precision Medicine
• Proportional Hazards Models
• Prospective Studies
• Survival Analysis
• Treatment Outcome