No clinical benefit of specific immunotherapy seen in lymphoma

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1. Compared to immunotherapy with keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF), specific vaccines with idiotypes (Id) plus GM-CSF and KLH demonstrated no difference in clinical outcomes.

2. Vaccinated patients who mounted specific anti-Id responses showed increased progression-free survival.

Evidence rating level: 1 (Excellent)

Study Rundown: Much of the recent development in cancer therapy has focused on immunotherapy, including both passive and active immune responses. MyVax, a vaccine composed of tumor immunoglobulins chemically coupled to KLH, is one such therapy. In a previous phase III clinical trial, MyVax was shown to make no statistically significant difference in progression-free survival (PFS) in previously untreated follicular lymphoma. The authors of this randomized, controlled trial found that there was no significant difference in either progression free survival or time to next therapy among patients taking MyVax compared to controls. Anti-Id humoral immune responses were seen in 41% of patients with a median PFS of 40 months, which was significantly greater than the median PFS observed in treated patients without Id-induced IRs and in those in the control arm. Based off of these results, the authors suggest that MyVax anti-Id IR responses may represent a better underlying prognosis or a possible therapeutic benefit for this subset of patients. These conclusions are strengthened by the randomized, controlled design of this study and its multi-center population.

Click to read the study in JCO

Click to see an accompanying editorial in JCO

Relevant Reading: Tumor-specific recombinant idiotype immunization after chemotherapy as initial treatment for follicular non-Hodgkin lymphoma

In-Depth [randomized controlled trial]: This was a multi-center, randomized trial. Eligible patients were diagnosed with previously untreated advanced-stage follicular lymphoma, who then received eight cycles of chemotherapy with cyclophosphamide, vincristine and prednisone. A total of 287 patients who had achieved sustained partial or complete remission were then randomly assigned at a ratio of 2:1 to either 7 months of MyVax or control immunotherapy. Anti-Id antibody responses were measured before each immunization. The primary end point was progression-free survival, and secondary end points antibody immune response and time to subsequent therapy for lymphoma. Median follow-up was 58 months. No significant difference was found between MyVax and control, with PFS 19 and 23 months, respectively (p = 0.297). Anti-Id antibody responses were observed in 41% of patients in the MyVax arm, with a median PFS of 40 months (compared to 16 months for the non-responders, p = 0.0003).

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