Rituximab does not improve survival of patients treated with M/VACOP-B plus radiotherapy in primary mediastinal large B-cell lymphoma (PMLBCL): An Italian phase II study of Intergruppo Italiano Linfomi (IIL)

Introduction: M/VACOP-B regimens in combination with involved-field radiotherapy (IFRT) seem to improve survival of PMLBCL. The superiority of R-CHOP over CHOP has been demonstrated in randomized trials. The addition of Rituximab to CHOP has also improved the survival of PMBLCL. Our study aimed to evaluate the effectiveness and safety of Rituximab added to M/VACOP-B regimens (R-M/VACOP-B) +/- IFRT in PMLBCL. Patients and methods: Forty-five patients (pts) with PMLBCL have been treated in 6 Italian centers between February 2002 and July 2006. The median age was 38yrs (range 17-66); 24/21 (53%) were females; 32 pts had stage IIand 13 IIE-IV; 42 (95%) had a bulky disease; LDH was increased in 31(69%) and 24(55%) had a superior vena cava syndrome. All pts were treated with standard MACOP-B (35 pts) or VACOP-B (10pts) regimens plus 6 cycles of Rituximab (375mg/m 2 ) given at weeks 3,5,7,9,11,13. Thirty-two pts (71%) received mediastinal IFRT at a median dose of 30-36 Gy. The response was evaluated in all pts after 6-12 cycles of R-M/VACOP-B and after IFRT. Results: The response rate after 6 cycles was CR/CRu=20 (45%), PR=24 (54%) and NR=1 (2%). Three/45 PR pts received an intensification with HDT-ASCT after 6 cycles due medical decision in spite of the planned protocol. At the end of 12 cycles, 26 pts witnessed a CR/CRu (62%), 15 a PR (36%) and 1 NR (2%). Eight/17 PR pts obtained a CR/CRu following IFRT for an overall CR/CRu rate of 34/42 (80%). Five patients (2 CR, 3 PR) relapsed within 19 months from end of therapy and died of progressive disease. After a median follow-up of 25months, the 2-year OS and PFS were 80% and 84%, respectively. In a our historical group of 92 pts with PMBCL treated with MACOP-B+IFRT without Rituximab the 5-yrs OS and PFS were 87% and 81% respectively. Discussion: R-M/VACOP-B are active therapeutic regimens devoid of severe toxicity in PMBCL. 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 may truly improve the response rate and survival of PMBCL