PS1090 OBINUTUZUMAB DOES NOT COMPROMISE MOBILIZATION AND ENGRAFTMENT OF AUTOLOGOUS PERIPHERAL BLOOD STEM CELLS IN LYMPHOMA PATIENTS: RESULTS FROM A FIL PROSPECTIVE PHASE II STUDY (THE GIOTTO STUDY)

Abstract

Background:Salvage immunochemotherapy and transplant consolidation is the standard treatment for young relapsed refractory (R/R) DLBCL. Many studies have demonstrated that Rituximab combined with second line chemotherapy do not permit to obtain satisfactory results particularly in patients previously treated with Rituximab (see Coral and Scholar study). Moreover these regimens do not affect negatively the stem cell mobilization.Aims:Patients with first R/R DLBCL were prospectively treated with a combination of Obinutuzumab‐DHAP (G‐DHAP). The primary end point study was to demonstrate an increase in the metabolic complete response (CMR) rate with this regimen. Secondary end points were stem cell mobilization, stem cell engraftment, overall survival and feasibility.Methods:In thisprospective, phase‐2, single‐arm trial (EudraCT2014–004014–17), R/R DLBCL patients received Obinutuzumab‐DHAP with the standard three doses (1000 mg) of Obinutuzumab in the first cycle ad then one dose for the remaining three cycles. The stem cells apheresis was programmed after the third or the fourth cycle. At the end of therapy a restaging was performed and patients with CMR were consolidated with BEAM/FEAM condictioning regimen and autologous stem cell transplantation (ASCT). The protocol provided an interim analysis after the first 29 patients enrolled to confirm the initial null hypothesis of obtaining at leasr 10/29 CMR.Results:At first interim analysis 29 patients were evaluated. The median age was 56 years, 17 patients had a primary refractory lymphoma and 12 were relapsed. Fifteen patients completed the four programmed cycles and were evaluated for CMR. Six patients obtained a CMR (6/29 patients: 21%), the number of CMR pre‐ASCT was lower than the level set for continuing the study. According to the results of the interim analysis study enrolment was stopped. The haematological toxicity was that expected with DHAP, obinutuzumab has not added toxicity. Extrahematologic toxicity > = 3 was reported in 9 patients.We have evaluated the peripheral blood progenitors harvest. Nineteen patients started stem cell mobilization, one failed mobilization (5%) and 18 patients mobilized (95%). Nine out 18 patients did not reinfuse and 9 reinfused: 7 (24%), after a median follow up of 24 months, are alive and without evidence of disease, 1 was in partial remission and 1 progressed immediately after transplant. The overall survival and progression free survival are reported in Figures 1 and 2.Sixteen patients (89%) mobilized after 1 or 2 apheresis and the other two patients after three or four. The mean number of CD34+ cells mobilized was 5.8, the median number was 5.5 (IQR: 5 – 6.75). The mean number of reinfused CD34+ cells in the 9 patients was 4.1, the median number was 4.1 (IQR: 3.5 – 5).Summary/Conclusion:The association of Obinutuzumab and DHAP did not pass the interim analysis because a lower rate of CMR reported in comparison with the hypothesis. To note that seven patients (4 refractory and 3 relapsed) among the nine transplanted are alive and free from disease after a median follow‐up of 24 months.imageObinutuzuamb associated with a standard mobilizing chemotherapy (DHAP) did not compromise stem cell mobilization and engraftment after ASCT in this group of DLBCL patients.