A Phase II Study of Yttrium-90-Ibritumomab Tiuxetan In Combination with a Fludarabine-Based Reduced Intensity Regimen Followed by Allogenic Stem Cell Transplantation In Patients with Relapsed or Chemorefractory CD 20 Positive Non-Hodgkin's Lymphoma.

The outcome of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) is very poor despite aggressive treatments or novel therapeutic agents. Allogenic STC (allo-STC) remains the only curative approach with an interesting reduced treatment-related-mortality (TRM) commonly associated with reduced intensity conditioning regimens (RIC).

Radio immunotherapy (RIT) as part of conditioning regimen for autologous stem cell transplantion (ASCT) as well as for allo-SCT has demonstrated its safety and many studies are now suggesting an improved outcome.

This phase II study (ClinicalTrials.gov: NCT 00607854) evaluated the safety and efficacy of Yttrium-90 ((90)-Y)-ibritumomab tiuxetan in combination with a fludarabine-based RIC followed by allo-SCT in patients with relapsed or chemorefractory CD 20 positive non-Hodgkin's lymphoma.

Patients with relapsed or refractory CD 20 positive NHL where eligible for the study if they had a sensitive disease (at least partial response) to the last salvage regimen and a suitable donor: related (RD) or unrelated donor (MUD or with a C or DQ mismatch).

Each patient received a single dose of ((90)-Y)-ibritumomab tiuxetan (0,4 mci/Kg on day -14) followed from day -6 by a combination of fludarabine (30 mg/m² d -6 to d -2), busilvex ((3,2 mg/Kg d -5 and d -4) and antithymocyte globulin (2,5 mg/Kg d -1). GVH prophylaxis was based on cyclosporine (CsA) alone or in combination with methotrexate (Mtx) in case of mismatched unrelated donor.

The trial was designed to enroll 30 evaluable pts and the study started on January 2008. At time of this writing, 27 pts have been included and we report the preliminary results of the first 14 consecutive pts.

The primary objective (PO) of the study was to evaluate the day 100 TRM. Secondary objectives were response (CR, PR) and event-free survival at 1 year.

Fourteen pts are evaluable for the PO. The median age was 55 years (35-60), and the sex ratio (M/F) 10/4. Prior disease was DLBCL (5), MCL (4), FL (5). Pts received a median number of 2 previous treatment regimens and all pts had undergone ASCT before. Median time between diagnosis and allo-SCT and between ASCT and allo-SCT were 39 mo (range 8 – 106) and 14, 5 mo (range 3–52) respectively. At time of transplant 10 pts were in CR and 4 in PR. There were 10 RD and 4 MUD transplants. All pts received peripheral blood stem cells transplantation and GVH prophylaxis with CsA alone.

Two pts died from a-GVH at day 40 and 117 post-transplant respectively with a TRM at day 100 of 7%. Both were in CR. The median time to ANC engraftment (ANC > 500/mm³) was 17 days (range 12 – 22) and time to platelets engraftment (Plt > 20.000/mm³) was 11 days (range 0–16). Acute GVH occurred in 7 pts with only 3 pts with grade ≥ 2. At day 100 after transplantation, 8 out of the 10 (80%) evaluable pts achieved a complete T-cell donor chimerism.

With a median follow-up of 10 month (range 6 – 26), 12 pts are alive and in CR. The estimated event-free survival at 1year is 86% (CI 78% - 94%).

((90)-Y)-ibritumomab tiuxetan is safe and well tolerated when used in combination with a fludarabine-based RIC regime. Preliminary data suggest that the TRM is not increased by adding RIT in this conditioning regimen.

Bouabdallah:Bayer Healthcare: The Trial has been partially sponsored by Bayer Healthcare. Off Label Use: Zevalin is off-label use in conditioning regimen in France.