Yttrium-90-Ibritumomab Tiuxetan (Zevalin) in Combination with a Fludarabine-Based Reduced Conditioning Regimen (RIC) Followed by Allogenic Stem Cell Transplantation for Advanced/Aggressive Non-Hodgkin's Lymphoma (NHL): A Prospective, Multicentre, Open Phase II Study

Abstract 3027

Patients (pts) with advanced/aggressive NHL who relapse after autologous stem cell transplantation (auto-sct) or who fail to respond to front-line chemotherapy have a very bad prognosis with a poor survival. We performed a prospective and multicentre study (Clinical Trials.gov, NCT 00607854) to evaluate the tolerability and the benefit of Zevalin added to a fludarabine-based RIC followed by allogenic stem cell transplantation (allo-sct) in pts with a poor prognosis lymphoma.

Between January 2008 and October 2010, 30 pts under 65 years old with NHL in relapse after at least 2 previous regimen with or without auto-sct underwent an allo-sct with this preparative regimen. The underlying disease was DLBCL (10 pts), MCL (9 pts) and low grade lymphoma (FL=9 and MZL=2). Patients had to be in CR or PR after the last salvage regimen (Cheson criteria) and to have a HLA-compatible (10/10) match-related (MRD) or unrelated (MUD) donor or 9/10 mismatched UD. GVH prophylaxis was based on CsA alone or in combination with Methotrexate in case of mismatch. The primary objective of the study was TRM at day 100.

All the pts are evaluable Twenty two were male (73%) and the median age was 57 (32–64). Twenty nine pts (97%) had prior auto-sct. Twenty pts were transplanted from a sibling donor, 8 from MUD and 2 pts had a C or DQ mismatch. At time of allo-sct, 18 pts were in CR and 12 pts in PR. Median time between diagnosis and allo-sct and between auto-sct and allo-sct was 36 mo and 18 mo respectively. Four pts died from a-GVH (n=2) at d 40 and 70, multi-organ failure (n=1) at d 117 and disease progression (n=1) at d 114 respectively. The TRM up to day 100 was 7% (n = 2). The median follow-up is 16 mo (9–40). All pts had a rapid and sustained engraftment. Twenty five pts are alive in CR. One pt died in CR (suicide) one year after transplant. The actuarial 3-year event-free and overall survival are 83% (± 6%). Estimated EFS at 2 years for the 3 different subgroups of diagnosis are 100% for FL and MZL, 89% (± 10%) for MCL and 70% (± 14%) for DLBCL.

We conclude that Yttrium-90-ibritumomab tiuxetan (Zevalin) in combination with a fludarabine-based regimen is safe with a very low TRM rate. The results we report here are in pts with a very bad prognosis are very encouraging with a very high response rate and survival.