R-CVP after radiotherapy improves progression-free survival in early-stage follicular lymphoma

BACKGROUND AND PURPOSE: The recently-updated TROG 99.03/ALLGLow5 multicentre randomised controlled trial showed that long-term progression-free survival (PFS) in early-stage (I-II) follicular lymphoma (ESFL) after involved-field radiotherapy (IFRT) was dramatically improved by adjuvant rituximab-cyclophosphamide/vincristine/prednisolone (R-CVP) but not CVP. Secondary analyses are presented here. MATERIALS AND METHODS: We analysed toxicity of RT and RT plus systemic therapy, outcomes for discontinuous stage II disease, second malignancy risks, prognostic impact of indeterminate bone marrow (BM) aggregates and the effect of rituximab on histological transformation. BM trephines from 55 patients from the pre-rituximab era were centrally reviewed. RESULTS: As previously-reported, 150 patients were randomised to IFRT (n = 75) or IFRT plus systemic therapy (n = 75). After 11.3 years median follow-up, IFRT + R-CVP was associated with improved PFS compared to IFRT or IFRT + CVP (HR 0.36, p = 0.01). Short-term RT-related grade I-II toxicity occurred in >90%, but toxicity after >6 months was rare. Worst acute systemic therapy toxicity was G1 (16 patients, G2 31 and G3 20) with 3 grade 3 neuropathies. R-CVP and CVP were equally toxic. Only 2 of 5 patients with non-contiguous stage II relapsed. Of 64 relapsed patients, 39 commenced salvage therapies and 17 had second progressions. Second malignancies showed no relationship to irradiated-volumes or systemic therapy use. Indeterminate BM aggregates did not worsen PFS. CONCLUSION: The improvement in PFS, reduced salvage therapy requirements, and prevention of histological transformation with R-CVP outweigh its significant but transient toxicity, supporting its justifiable use. Patients with indeterminate BM lymphoid aggregates or non-contiguous stage II FL may merit consideration for curative-intent treatment.