Rituximab combined with M/VACOP-B and radiotherapy in primary mediastinal large B-cell lymphoma (PMLBCL): A prospective italian phase II study of Intergruppo Italiano Linfomi (IIL)

Introduction. Third generation regimens such as MACOP-B or VACOPB (M/VACOP-B) in combination with involved-field radiotherapy (IFRT) seem to improve lymphoma-free survival of PMLBCL. The superiority of R-CHOP over CHOP-like regimens has been demonstrated in younger low risk DLBCL. Recently, the addition of Rituximab to CHOP has also improved the survival of PMBLCL. Aims. To evaluate the effectiveness and safety of Rituximab added to the standard M/VACOP-B regimens (R-M/VACOP-B) ± IFRT in PMLBCL. Patients and Methods. At this time, a total of 45 patients with PMLBCL have been treated in six participating centers between February 2002 and July 2006. The median age was 38 years (range 17-66); 24/21 (53%) were females; 32 patients had stage II and 13 stage IV; 42 (95%) presented a bulky disease; LDH was increased in 31 (69%) and 24(55%) had a superior vena cava syndrome. According to the age-adjusted IPI score, 30 patients had an IPI = 0-1 and 15 an IPI = 2-3. All patients were treated with standard MACOP-B (35 patients) or VACOP-B (10 patients) regimens plus six cycles of Rituximab (375 mg/m2 ) given at weeks 3,5,7,9,11,13. Thirty-one patients (69%) received mediastinal IFRT at a median dose of 36 Gy. The response was evaluated in all patients after 6 cycles of chemo-immunotherapy, at the end of the planned chemotherapy and after IFRT. Results. The response rate after 6 cycles of the planned R-M/VACOP-B regimen was CR/CRu = 20 (44%), PR=24 (53%) and NR=1 (3%). Six/45 patients received an early intensification therapy followed by HDT-ASCT because considered low responders (less than PR or progressive disease) during M/VACOP-B chemotherapy. At the end of the chemo-immunotherapy program, 28 patients witnessed a CR/CRu (70%) and 17 a PR (30%). Nine/17 PR patients obtained a CR/CRu following IFRT for an overall CR/CRu rate of 82% (37/45). Three patient relapsed at 12, 12 and 19 months from CR and died of progressive disease despite salvage therapy. After a median follow-up of 25 months, the 3-year OS and PFS were 80% and 78%, respectively. No significant differences in terms of PFS and OS were associated with the IPI score. No additional toxicities related to Rituximab infusion were observed. Discussion. R-M/VACOP-B are active therapeutic regimens devoid of severe toxicity for the management of patients with PMLBCL. Consolidation radiotherapy seems to improve the quality of response. Further studies are required to demonstrate if the addition of Rituximab to M/VACOP-B regimens might improve the overall rate of response and survival.