Comparison of the Sequential High-Dose Chemotherapy Followed by Autologous Stem Cell Support with and without Rituximab in Relapsed and Refractory Aggressive Non-Hodgkin’s Lymphoma.

Introduction: Combination chemotherapy can cure patients (pts) with Non-Hodgkin’s lymphoma (NHL), but those with relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell support (ASCT) can improve the outcome of these pts. Rituximab demonstrated encouraging activity in aggressive NHL and showed low toxicity in the setting of combined immunochemotherapy. To investigate the influence of addition of rituximab to the intensified salvage program followed by a final myeloablative course with stem cell reinfusion we compared the group of patients treated with this program - immuntherapy group (IT) with the standard therapy group (ST) of patients treated with the same program without rituximab.

Patients and methods: Eligibility criteria for both groups were as follows: age 18–67 years, eligibility for HDCT, histologically proven CD20+ relapsed or progressive NHL. Treatment program starts with two cycles DHAP (dexamethasone, cytarabine, cisplatin); pts with PR or CR receive cyclophosphamide (4g/m2) followed by PBSC harvest; methotrexate 8g/m2 and vincristine 1,4mg/m2; and etoposide 2g/m2. The final myeloablative course is BEAM followed by ASCT. Pts in IT received additionally rituximab (375mg/m²) to the each chemotherapy cycle.

Results: In the immuntherapy and standard therapy group were enrolled 23 and 57 pts, respectively. There were 18 (78%) IT and 34 (60%) ST pts with relapsed and 5 (22%) IT and 23 (40%) ST pts with refractory disease. The majority of pts in both groups received CHOP-like regimens as first line treatment (91% IT vs. 79% ST). The response rate at the final evaluation for all patients was in IT 61% (52% CR and 9% PR) and in ST 43% (32% CR and 11% PR). The overall response rate (OR) for patients who responded to 2 cycles DHAP was in IT 83% (71% CR and 12% PR) and in ST 59% (44% CR and 15% PR). The therapy toxicity was tolerable and comparable in both groups.

Conclusion: The preliminary results suggest better therapy outcome in patient with sequential high-dose chemotherapy with rituximab compared to pts treated with the same therapy regimen without additional antibody. The combination regimen allows effective mobilization of stem cells. The tolerability of the final myeloablative BEAM was in both groups not affected by rapid sequential administration of DHAP and high doses of cyclophosphamide, methotrexate, etoposide and rituximab. The toxicity was tolerable in both groups. The full results of match pair and multivariate analysis as well as OS and FF2F will be presented.