Five-year overall survival for high-risk
Follicular Lymphoma International Prognostic Index
follicular lymphoma is only approximately 50% compared with 90% for low risk. To evaluate an approach to improve upon this poor outcome, we completed an exploratory phase II trial of intensified treatment for patients with intermediate and high-risk
follicular lymphoma. Front-line treatment with chemo-
immunotherapy consisting of
rituximab,
cyclophosphamide,
vincristine,
doxorubicin, and
prednisone was followed by radio-
immunotherapy with 90-Yttrium
ibritumomab tiuxetan consolidation, and 2 years of
rituximab maintenance. The 5-year overall survival for intermediate and high-risk patients was 88% and 83%, respectively. Of 33 enrolled patients, 3 were off study before receiving radio-
immunotherapy. Three months post radio-
immunotherapy, 28/33 (85%) patients had achieved complete response including 6 patients who had only a partial response to chemo-
immunotherapy and converted to complete response after radio-
immunotherapy. The 5-year progression-free survival for intermediate and high risk was 79% and 58%, respectively. Nine of 19 patients with molecular markers patients remain in molecular and clinical complete remission with a median follow-up of 48 months (range 3-84 months). Post radio-
immunotherapy, hematologic toxicities were mostly grade 1 and 2. However, asymptomatic grade 3 or 4
thrombocytopenia and
neutropenia occurred in 11%-36% and 10%-24% of patients, respectively.
Myelodysplastic syndrome occurred in 1 patient 4 years post treatment. Whereas many patients had prolonged B-cell reduction and low
immunoglobulin levels post treatment, previous immunities to
rubella were maintained. More aggressive upfront approaches such as this may benefit higher risk
follicular lymphoma, but confirmatory trials are required. http://www.clinicaltrials.gov: NCT01446562.