Rituximab-CHOP (R-CHOP) and Radiotherapy (RT) for Primary Mediastinal Large B-Cell Lymphoma (PMLBCL).

Background: MACOP-B or even chemotherapy (CT) with consolidation high dose therapy with autologous stem cell support (HDT-ASCT) have been considered superior to CHOP in PMLBCL. However, in the absence of randomized trials, there is no established optimal treatment for these patients. The role of R-CHOP in PMLBCL, which usually affects young patients, has not been established.

Aims: To evaluate the efficacy of R-CHOP±RT in PMLBCL and to compare this approach with CHOP±RT administered to historical controls.

Patients and Methods: Between 1994 and 2006, 74 patients with PMLBCL were treated in 6 participating centers. R-CHOP displaced CHOP in the treatment of PMLBCL at a given timepoint in each center. Thus 31 consecutive patients who received R-CHOP, were compared with 43 consecutive historical controls, who had been treated with CHOP prior to that point.

Results: The median age of the patients was 30 years (17–82), only 2 patients (3%) were older than 60 years, and 47/74 (64%) were females. All individual IPI parameters as well as B-symptoms were also balanced between the two groups, with the exception of performance status. The median follow-up of currently alive patients was 28 and 73 months for patients treated with R-CHOP±RT and CHOP±RT respectively, the complete response (CR/CR_u) rate was 97% vs 67% (p=0.002), and the overall response rate was 100% vs 79%, respectively (p=0.007). All relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 93±5% vs 53±8% for patients who received R-CHOP±RT vs CHOP±RT (p=0.0006). Within the subgroup of patients with L/LI risk IPI, the corresponding 3-year FFS rates were 95±5% vs 58±10% (p=0.007), while they were 90±9% vs 45±12% (p=0.03) among patients with HI/H risk IPI. The 3-year event free survival (EFS) for all patients was 90±5% vs 51±8% (p=0.001). The 3-year overall survival (OS) was 97±3% vs 67±7% (p=0.008), while the 3-year lymphoma specific survival (LSS) was 100% vs 67±7% (p=0.002).

Conclusions: R-CHOP and RT provided impressive results with no cases of primary refractory disease, no lymphoma-related deaths and only 2 failures recorded so far after a median follow-up of 28 months among 31 patients. Patients treated with R-CHOP had significantly higher CR, FFS, EFS, OS, and LSS rates, when compared with CHOP-treated historical controls. Based on these results we continue to treat PMLBCL patients with R-CHOP and RT, avoiding more intensive strategies. Further studies are warranted to investigate whether RT is needed after R-CHOP, especially in the case of a negative post-chemotherapy PET-scan.