Rituximab Combined with M/VACOP-B and Radiotherapy in Primary Mediastinal Large B-Cell Lymphoma (PMLBCL): A Prospective Italian Phase II IIL Study.

Background: Third generation regimens such as MACOP-B or VACOP-B (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 recently demonstrated in younger low risk DLBCL. Recently, the addition of Rituximab to CHOP has also improved survival in 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: A total of 40 patients with PMLBCL has so far been treated in the six participating centers between February 2002 and July 2005. The median age was 38 years (range 17–54); 21/19 (53%) were females; 30 patients had stage II and 10 stage IV; 38 (95%) presented a bulky disease; LDH was increased in 26 (65%) and 21(53%) had a superior vena cava syndrome. According to the age-adjusted IPI score, 24 patients had an IPI = 0–1 and 16 an IPI = 2–3. All patients were treated with standard MACOP-B (30 patients) or VACOP-B (10 patients) regimens plus six cycles of Rituximab (375mg/m²) given at weeks 3, 5, 7, 9, 11 and 13. Twenty-six patients (65%) received mediastinal IFRT at a median dose of 36 Gy. The response was evaluated in all patients after six cycles of chemo-immunotherapy, at the end of the planned chemotherapy and after IFRT.

Results: The response rate after six cycles of the scheduled R-M/VACOP-B regimen was CR/CRu = 20 (50%), PR = 19 (47%) and NR = 1 (3%). Eight of the 40 patients received a second line therapy followed by HDT-ASCT (6/8 patients) because considered as low responders (PR = 7 and NR = 1). At the end of the chemo-immunotherapy program, 28 patients witnessed a CR/CRu (70%) and 12 a PR (30%). Seven of the 12 PR patients obtained a CR/CRu following IFRT for an overall CR/CRu rate of 87% (35/40). After a median follow-up of 13 months, the 2-year OS and PFS are 75% and 78%, respectively. No additional toxicities other than those related to chemotherapy were observed during and after Rituximab infusion.

Conclusions: R-M/VACOP-B are active therapeutic regimens devoid of severe toxicity for the management of patients with PMLBCL. The addition of Rituximab to M/VACOP-B regimens does not seem to improve the lymphoma-free survival of this group of patients. An update of these results on a broader number of patients will be presented at the meeting.