Excellent Outcome with Rituximab-CHOP (R-CHOP) Combined with Radiotherapy (RT) in Primary Mediastinal Large B-Cell Lymhoma (PMLBCL).

Introduction: Combination chemoptherapy regimens such as CHOP and MACOP-B with or without RT are considered the standard first-line treatment for PMLBCL patients. Consolidation with high dose therapy and autologous stem cell support (HDT-ASCT) at first remission is an alternative approach for this young population. However results are not optimal. Given the superiority of R-CHOP over CHOP in elderly patients with diffuse large B-cell lymphoma, the role of Rituximab added to first-line chemotherapy in younger patients is not clear.

Aims: In this study we evaluate the effectiveness of R-CHOP±RT in PMLBCL and we compare the results of this strategy to CHOP±RT in historical controls.

Patients and Methods: A total of 46 patients with PMLBCL were treated in two participating centers between 1994 and 2004. At a given timepoint R-CHOP replaced CHOP in both centers. Thus, 31 consecutive historical controls were treated with CHOP prior to that point and were compared to 15 patients who received R-CHOP thereafter.

Results: The median age of the patients was 31 years (17–58) and 32/46 (70%) were females. Baseline characteristics between the R-CHOP and CHOP groups were well balanced, including age-adjusted IPI [ ≥2 in 40% of R-CHOP and 42% of CHOP-treated patients (p=0.90)]. Complete response (CR) was achieved in 100% in the R-CHOP±RT vs 61% in the CHOP±RT group (p=0.009). No patient has relapsed after R-CHOP, while all relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 100% and 47±9% for patients treated with R-CHOP±RT and CHOP±RT respectively(p=0.005). Within the subgroup of patients with L/LI risk IPI the corresponding 3-year FFS rates were 100% vs 61±11% (p=0.059), while they were 100% vs 26±13% (p=0.02) among patients with HI/H risk IPI for R-CHOP±RT and CHOP±RT respectively. The 3-year event free survival (EFS) was 93±7% vs 47±9% (p=0.02). The 3-year overall survival was 93±7% vs 47±9% (p=0.27), while the 3-year lymphoma specific survival was 100% vs 67±9% (p=0.049) for the R-CHOP and CHOP groups respectively.

Conclusions: R-CHOP±RT exhibited impressive efficacy with no failures among 15 patients. CR and FFS rates were significantly better in favor of R-CHOP compared to CHOP-treated historical controls. EFS and lymphoma specific survival were also improved. Based on these data, our standard approach for PMLBCL patients is the application of R-CHOP±RT. Furthermore the addition of Rituximab to front-line treatment might overcome the need for more aggressive strategies such as consolidation with HDT-ASCT in this patient population.