The impact of initial treatment of advanced stage indolent lymphoma on the risk of transformation

Abstract

7510 Background: The impact of initial treatment of indolent non-Hodgkin’s lymphoma (NHL) on the risk of transformation (TR) to aggressive NHL is unknown. High LDH and advanced stage at diagnosis have been shown to be predictive for TR; however, the effect of initial treatment is difficult to estimate as most series included heterogenous patient (pts) populations. Methods: As part of a large retrospective analysis examining TR (n = 698), we identified pts from 2 consecutive phase II studies conducted at the British Columbia Cancer Agency. Both studies had identical inclusion criteria: diagnosis of indolent NHL, no prior treatment, age16–60 y and advanced stage disease (III/ IV or I/ II with B symptoms or bulky disease ≥10cm). The first study included use of BPVACOP (bleomycin, cisplatin, etoposide, doxorubicin, cyclophosphamide,vincristine and prednisone, followed by involved field irradiation (RT) to original nodal sites of lymphoma. The second used combination alkylator-purine analogue (cyclophosphamide- cladrabine or fludaribine and prednisone). The definition of TR was based on either histological confirmation (HIST) or clinical features (CLIN), defined as one or more of the following: rapid discordant nodal or extranodal growth; sudden rise in LDH to > 2 x previous baseline; involvement of unusual extranodal sites; or hypercalcemia. Results: 260 pts were identified. BPVACOP+RT (n = 140), alkylator-purine analogue (n = 120). Median age 46 y (19–60). Follicular histology in 133 (94%) and 105 (87%), respectively. The majority were stage III/IV (89%) with equal proportions in each cohort. With a median follow-up (FU) for living pts of 90 months (1–225), 26 (18%) pts treated with BPVACOP+RT developed TR, 16 of which were confirmed with biopsy, versus 32 (27%) in the alkylator-purine group, of which 18 had biopsy confirmation. The 5 y risk of TR for BPVACOP+RT was 9% compared to 24% for the alkylator-purine analogue group (p < 0.0095). The annual risk of TR through 10 y of FU was 1.5% and 3.0%, respectively. The post-TR 5 y OS of all 58 pts with TR was 19%. Pts with TR based on CLIN vs HIST criteria did not differ in their outcome. Conclusions: The use of an anthracycline-based regimen as initial treatment for advanced stage indolent NHL is associated with a marked reduction in the risk of future TR. No significant financial relationships to disclose.