The Addition of Ibritumomab Tiuxetan (IT) to the ATG/TLI Preparative Regimen Is Safe and May Enhance Post-Transplant Response and Outcomes for Patients with Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

Background: Nonmyeloablative allogeneic stem cell transplantation (NMT) is an effective salvage therapy in relapsed or refractor non-Hodkgin's lymphoma (R/R NHL) but is limited by significant transplant-related mortality (TRM). Total lymphoid Irradiation (TLI) and anti-thymocyte globulin (ATG) conditioning is well tolerated with low TRM and results in significant anti-tumor activity with low rates of graft versus host disease (GVHD). However durable remissions are limited to patients in remission at the time of transplant. We hypothesized that when IT is added to ATG/TLI conditioning this would convert patients (Pts) with stable disease/partial response (SD/PR) to partial response/complete response (PR/CR) and result in improved outcomes after ATG/TLI conditioning and allogeneic transplantation. Methods: In this phase 2 study, Pts with CD20+ R/R NHL underwent NMT using G-CSF mobilized peripheral blood stem cells from an HLA-matched (9/10 or better) donor. Included in the category of CD20+ R/R NHL were follicular grade I, II, III (FL), marginal zone, mantle cell (MCL), diffuse large B cell (DLBCL), small lymphocytic lymphoma for which standard curative therapy does not exist or is no longer effective. To be eligible patients had to be older than 18 years of age with Karnofsky performance status (KPS) of ≥ 60.. Patients must have had at least one prior chemotherapeutic regimen and have had anything less than a CR (PR, SD or progressive disease) to their last regimen. Conditioning consisted of rituximab (250 mg/m2, days -21 and -14), IT (0.4 mCi/ kg, day -14), TLI and ATG (800 centigray in 10 fractions and 1.5 mg/kg, respectively, from days -11 to -1). GVHD prophylaxis consisted of cyclosporine (6.25 mg/kg po bid, days -3 to +56 followed by taper) and mycophenylate mofetil (15 mg/kg po, days 0 to +28).The primary endpoint was response conversion rate (SD/PR to PR/CR) monitored with Simon's optimal 2 stage design. Response was assessed by CT or PET/CT at 60 days post-transplant and then every 4 months per International Workshop Lymphoma Response Criteria. Secondary endpoints were time-to-chimerism, 2-year (2Y) overall survival (OS) and event free survival (EFS), toxicity assessment, and GVHD incidence. Time-to-event endpoints were estimated by the Kaplan- Meier method. Toxicities were graded according to the NCI CTCAE v4.0. Results: Sixteen Pts were enrolled. Fifteen Pts underwent NMT and are evaluable for toxicity. One Pt died prior to conditioning. Eleven Pt