90Yttrium Ibritumomab Tiuxetan (Zevalin) Combined with BEAM (Z -BEAM) Conditioning Regimen Plus Autologous Stem Cell Transplantation in Relapsed or Refractory Follicular Lymphoma. GELA Phase II Study.

Autologous stem cell transplantation (ASCT) is widely used in relapsed or refractory low grade lymphoma with conditioning regimen including chemotherapy with or without total body irradiation (TBI). Radiolabelled immunotherapy 90Yttrium ibritumomab tiuxetan (Zevalin) is effective in B-cell lymphoma and delivers targeted radiation without TBI toxicity. To take advantage of this antilymphoma effect, conventional dose of 90Yttrium ibritumomab tiuxetan 15 MBq/kg (maximum 1200 MBq, total dose) was given without dosimetry day -14 before ASCT and combined to standard BEAM regimen starting at day -7. The goal of this phase II study was to evaluate efficacy and toxicity of Z BEAM. Patients < 65 years with CD20+ low grade B cell Lymphoma in 1st or 2nd relapses, or not achieving complete remission after first line treatment were included in the trial. They had to be chemosensitive to last salvage therapy, no more than three lines of treatment and eligible for ASCT. The primary end point was to detect a 2 yrs EFS at least 80%. Hematological reconstitution was evaluated after transplant and during the first year follow up. From 3/2005 to 8/2006, 77 patients were included. Patients characteristics at inclusion: 90% follicular lymphoma, median age 53 yr. (31–64), FLIPI <3, 74%, bone marrow involvement, 22%. Median delay between first line and ASCT was 31 months and median last salvage and ASCT 4.4 months. Response rate before ASCT were CR 36%, CRu 41%, PR 22%, stable 1%. As first line treatment, all pts received mostly CHOP associated in 29 cases with rituximab; 29 patients had relapsed and received a second line chemotherapy with rituximab in 22 cases; 48 patients who did not achieved remission after first line treatment received another line of chemotherapy before ASCT. Overall, among the 77 pts last salvage chemotherapy regimen included rituximab in 74 pts. The haematological reconstitution after Z-BEAM followed by ASCT in 75 pts was: time to neutrophils > 1G/L 12 days (9–35), time to platelets >20 G/L 12 days (3–42). Median number of platelets transfusions 4; red blood cell transfusions 2. Grade 3-4 toxicities were: infection 83%, mucositis 47%, pulmonary 4%. Safety data indicated 35 serious adverse events in 24 patients that did not appear to significantly differ from those usually seen after ASCT. No toxic death was observed. At week 12 and 42 after ASCT, median haemoglobin level were 11.6 g/dl and 11.3 g/dl, median platelets counts was 111G/L and 148 G/L, leucocytes counts 3.48 G/L and 4.80 G/L respectively. Only 5 events were reported. After a minimum follow up of one year for all patients, estimated 2 years EFS is 93%. Updated results on survival will be reported. Conclusion: Z BEAM is a safe conditioning regimen which can be used for B cell lymphoma. Longer follow up is necessary to evaluate long term toxicity and efficacy. Further randomized study are warranted.