Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma

Abstract

Background: Follicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response is typically shorter than that patient's first complete response. Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven.

Methods: Thirty-three consecutive follicular lymphoma patients in first relapse received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a second complete response were vaccinated periodically for more than 2 years with autologous lymphoma-derived idiotype protein vaccine. Specific humoral and cellular responses were assessed, and patients were followed for disease recurrence. Statistical tests were two-sided.

Results: Idiotype vaccine could be produced for 25 patients who had a second complete response. In 20 patients (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was detected. The median duration of the second complete response has not been reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20 responders relapsed while undergoing active vaccination. All responders with enough follow-up for the comparison to be made experienced a second complete response that was statistically significantly (P<.0001) longer than both their first complete response (18 of 18 patients) and than the median duration of a CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The five nonresponders all had a second complete response that was shorter (median = 10 months; range = 8-13 months) than their first complete response (median = 17 months; range = 10-39 months).

Conclusions: Idiotypic vaccination induced a specific immune response in the majority of patients with follicular lymphoma. Specific immune response was associated with a dramatic and highly statistically significant increase in disease-free survival. This is the first formal demonstration of clinical benefit associated with the use of a human cancer vaccine.