A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.

The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet many are denied potentially curative high-dose regimens due to concerns of excessive toxicity with stem cell transplantation in this age group. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be ideal for older adults requiring high-dose therapy. We have treated 24 patients with relapsed or refractory B-cell NHL aged ≥60 years using high-dose I-131-tositumomab (GlaxoSmithKline) and ASCT on a phase II trial. Patients were required to have a performance status of 0–1, acceptable organ function, ≥2x106 CD34+ cells/kg collected, and <20 Gy prior radiation to critical organs. Patients with splenomegaly or tumor bulk over 500cc were required to undergo further cytoreduction or splenectomy in order to optimize biodistribution of the radiolabeled antibody. Patients without evidence of disease at the time of therapy were excluded. All pts underwent outpatient dosimetry using tositumomab (1.7 mg/kg) labeled with 5–10mCi I-131 followed by serial quantitative gamma camera imaging and patient and organ-specific dosimetry. Patients then received individualized infusions of I-131-tositumomab (1.7 mg/kg) to deliver 25–27Gy to the critical normal organ receiving the highest radiation dose followed by ASCT. Between 12/1/99 and 4/29/05 24 pts were enrolled on this study. Baseline characteristics included: median age at ASCT = 64 yrs (range 60–76 yrs), male = 15/24, median number of prior regimens = 4 (range 2–14), chemoresistant disease (defined as < a partial response to the most recent regimen) = 13/24, Stage III/IV=100%, >1 extranodal site = 21%, elevated LDH at treatment = 46%, IPI score at transplant 3–5 = 46%, Histology: diffuse large B-cell (DLBCL)=9 pts (with 4/9 transformed from follicular lymphoma [FL]), mantle cell (MCL)=8 pts, FL=6 pts, and marginal zone (MZL) 1 pt. The median I-131 activity administered was 525 mCi (range 328–1154 mCi) with dose limiting organs being lung, liver, and kidney in 12, 8, and 4 patients, respectively. The therapy was well tolerated with no treatment-related deaths, and no grade 3–4 Bearman toxicity. NCI CTC non-hematopoeitic toxicities by day 100 included: Grade 4=2/24 and Grade 3=17/24. The median time after ASCT for recovery of platelets > 20K and neutrophils >500 was 10 and 15 days, respectively. Sixteen of 24 pts remain alive (67%) and 10 (42%) are alive and progression-free with a median follow up from ASCT of 2.2 yrs (range 1 mo.–4.9 yrs.) for survivors. The estimated 3-year overall and progression-free survival are 56% and 37%, respectively. Surviving patients include 6/8 with MCL, 5/7 with FL/MZL, and 5/9 with DLBCL as well as 9/13 with chemoresistant disease. Myeloablative I-131-tositumomab with ASCT is a well-tolerated and effective transplant option for older adults with high-risk, relapsed B-NHL, though longer follow-up and additional pts will be needed to confirm the reproducibility and durability of these findings.