UP-FRONT AUTOLOGOUS STEM CELL TRANSPLANTATION BRINGS SURVIVAL BENEFIT TO PATIENTS WITH POOR-RISK FOLLICULAR LYMPHOMA

Sborník

Background. Intensive frontline therapy of follicular lymphoma remains controversial. But in the era of conventional chemoimmunotherapy, long-term progression- free survival of high-risk patients is poor and drops to only 30% in 5 years. Aims. A retrospective analysis of FL patients with unfavorable prognostic features receiving up-front autologous stem cell transplantation and comparison with anthracycline-based regimens. Methods. We studied 164 patients with newly diagnosed FL who met the GELF criteria. Forty (24%) were treated with ASCT (conditioning BEAM 200) due to high-risk disease (FLIPI, B2M, s- TK, bulky). Frontline therapy with chemotherapy only (CHT) was administered to 124 (76%) patients: CHOP/CHOP-like regimen to those with low-risk FL (n=95) and intensive protocol (Promace-Cyta-BOM/adequate intensity protocol) to intermediate-risk patients. Rituximab was added to frontline therapy in 60% and 56% of cases in ASCT and CHT group, respectively (p=ns). Maintenance immunotherapy was applied in 30% (ASCT) and 41% (CHT), p=0.22. ASCT patients shared more unfavorable prognostic features than CHT group: H-FLIPI (66% vs 34%, p=0.001), bulky disease >7cm (81% vs 51%, p=0.001), advanced clinical stage (95% vs 80%, p=0.02), elevated B2M (64% vs 39%, p=0.007). ASCT patients were significantly younger (median age 46 vs 57 years, p<0.01). Results. Complete remission rates were 93% and 81% in ASCT and CHT group, respectively (p=ns). Molecular CR was achieved in 89% of ASCT patients and 81% of CHT group (p=ns). After a median follow-up of 87 months (7.3 yrs), 29/40 (73%) ASCT patients are alive in the 1st CR as compared with only 68/124 (55%) in CHT group. Five-year PFS was 76% (95% CI 0.62-0.90) and 56% (95% CI 0.47-0.66, p=0.018) in ASCT and CHT group, respectively. Five-year overall survival of 95% (95% CI 0.88-1.00) in ASCT group was superior to that of 84% (95% CI 0.77-0.91, p=0.024) in CHT arm. Subanalysis of 93 patients treated with rituximab showed higher proportions of relapses and deaths in CHT group (22 events in 69 patients) than in ASCT group (4 events in 24 patients, p=0.048). Five-year PFS was higher in ASCT (86%, 95% CI 0.71- 1.00) than CHT group (63%, 95% CI 0.51-0.76). Despite 23% difference in 5- year PFS in favor of ASCT, statistical significance was not achieved (p=0.08). There was no difference in OS in rituximab treated patients; only 2 (8%) ASCT patients died as compared to 10 (14%) deaths in CHT group (p=0.13).Longterm toxicity in ASCT arm is acceptable. So far, no secondary MDS or AML have been observed; during the follow-up (median 100 months), only 4 patients died (2 lymphoma, 1 prostate cancer, 1 pneumonia). Conclusions. Frontline ASCT is very effective in high-risk FL patients. This approach overcomes multiple negative prognostic features of the disease and leads to superior survival compared to lower-risk patients treated with chemotherapy only.Supported by grants from Czech Ministry of Education (MSM 6198959205) and Faculty of Medicine and Dentistry, Palacky University Olomouc (LF-2011-006).

Haematologica, 2012; 97(s1):  16