90Y-ibritumomab tiuxetan, fludarabine, busulfan and anti-thymocyte globulin reduced intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas
Mené en France sur 31 patients atteints d'un lymphome non hodgkinien de stade avancé en échec thérapeutique, cet essai évalue la toxicité et l'efficacité de l'ibritumomab tiuxétan [90Y] en complément d'une greffe allogénique de cellules souches à conditionnement atténué (durée médiane de suivi : 32 mois)
Background : patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous-SCT have a poor prognosis. Allogeneic stem-cell transplantation after reduced intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of 90Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of 90Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. This study was registered at www.clinicaltrials.gov as #NCT00607854. Patients and Methods : Thirty one patients with advanced lymphoma from 5 distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for non-relapse mortality (NRM) at day 100 post-transplant that was the primary end point. Results : With a median follow-up of 32 months (range, 29 to 60 months), the 2-year event-free and overall survivals of the whole study group were both 80% (95 CI, 60.8% to 90.5%) The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI, 0.2%-14.9%) and 13.3% (95% CI, 5.4%-33.2%) respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI, 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic GVHD were 27% and 14%, respectively. Conclusions : For chemosensitive advanced high-risk B-cell lymphoma, the addition of 90Y-Ibritumomab tiuxetan to a reduced-intensity conditioning regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective.