HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION IN FIRST LINE TREATMENT FOR HIGH-RISK DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: AN INTENTION TO TREAT-ANALYSIS

Background: The combination of Rituximab and CHOP (R-CHOP) is\r\nconsidered to be the standard treatment for patients (pts) with newly diagnosed\r\ndiffuse large B-cell lymphoma (DLBCL). Treatment results are still unsatisfactory\r\nin a significant proportion of patients, particularly in those with a high-risk\r\ndisease defined by the IPI score. The use of high-dose chemotherapy with\r\nautologous stem-cell transplantation (ASCT) is standard clinical practice for\r\npatients with relapsed/refractory DLBCL, while its significance as consolidation\r\nin first-line treatment remains unclear.\r\nAims: We analyzed safety and effectiveness of R-CHOP followed by salvage\r\nchemotherapy and ASCT for patients with young (<65 years) high-risk DLBCL,\r\ndefined by an age-adjusted IPI score of 2/3, for whom from 2004 on our\r\ninstitutional guidelines recommended ASCT as consolidation. We analyzed\r\nprognostic factors in this group.\r\nMethods: The treatment program consisted of 4 cycles R-CHOP-14 followed\r\nby 3 cycles of a DHAP-like salvage regimen, R-MICMA (Sorà et al, Cancer\r\n2006; 106: 859), and consolidation with Busulfan-Melphalan supported with\r\nASCT. We observed 76 consecutive patients (median age 50 years, range 15-\r\n64 years; 32 females and 44 males) diagnosed between May 2004 and January\r\n2013 with DLBCL who had an age-adjusted IPI score of 2 or 3. Response was\r\nassessed according to Cheson criteria (Cheson et al, JCO 1999; 17:1244).\r\nResults: Nine of 76 patients (12%) were not eligible for the treatment program\r\nthat included ASCT. Reasons were important comorbidities in 6 pts (1 cardiac, 2\r\nneurologic, 1 hepatic, 1 hematologic, 1 renal) and start of another treatment\r\nregimen (CODOX-M/IVAC in the suspicion of a Burkitt lymphoma) in 3\r\npts. Response after 4 cycles R-CHOP was CR/CRu in 40/67 pts (60%), PR in\r\n21/67 pts (31%) and NR in 6/67 (9%). Sixty-one patients went on to salvage\r\nchemotherapy with R-MICMA, while 6 pts in CR/CRu continued R-CHOP, and 53\r\npts were transplanted. Reasons not to proceed to transplant were progressive\r\ndisease (3 pts), infections (3 pts), mobilization failure (1 pt) and patient’s decision\r\n(1 pt). The 3-year EFS and OS of the entire group of 76 patients were 67% (95%\r\nCI, 55-76) and 71% (95% CI, 59-80%), respectively. The 3-year EFS and OS of\r\ntransplanted patients were 70% (95% CI, 55-80) and 76% (95% CI, 62-85).\r\nFactors associated with inferior EFS were age-adjusted IPI score (2 vs. 3,\r\np=0.004) and disease status after 4 cycles R-CHOP (p=0.01) in univariate and\r\nmultivariate analysis. These differences were also retained in the group of patients\r\nwho received ASCT, with a three-years EFS of 78% in pts with an age-adjusted\r\nIPI score 2 vs 46% in pts with an age-adjusted IPI score 3 (p=0.003), suggesting\r\nthat ASCT is insufficient for highest risk patients.\r\nSummary and Conclusions: Our findings of an intention-to-treat, single centre\r\nexperience indicate that 88% of patients with high-risk DLBCL and age <65\r\nyears are eligible for a treatment strategy that includes ASCT, and 70% will\r\neventually receive ASCT as part of their first-line treatment. Consolidation with\r\nupfront ASCT for high-risk DLBCL is a feasible and promising therapy also in\r\nthe Rituximab era, but there are still subsets of patients that continue to have\r\na poor prognosis despite ASCT, and addition of new biologic drugs, as tyrosine\r\nkinase inhibitors, have to be tested to improve outcome in these patients.