Tositumomab and Iodine I-131 Tositumomab (Bexxar® therapeutic regimen) for Non-Hodgkin's Lymphoma Patients Who Progressed After Treatment with Rituximab: Long Term Follow-up of a Multi-Center Phase II Study.

Patients with indolent lymphoma generally require a number of therapies to address the relapsing course of disease and it is therefore important to provide long-term safety and efficacy data for novel therapeutics. We evaluated such data from the original phase II trial of the tositumomab and iodine-131 tositumomab therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab

From July 1998 to November 1999, 40 patients with a median age of 57 years (24 rituximab nonresponders: 11 with response <6 months, and five with response ³6 months) received a therapeutic dose (0.65 to 0.75 Gy) of iodine-131 tositumomab based on total-body dosimetry. Adverse prognostic characteristics included elevated lactic dehydrogenase in 31% and high or high-intermediate International Prognostic Index score in 21% of patients. Thirteen patients (32%) had tumor masses >7 cm and 20 patients (50%) had tumor masses >5 cm. The median number of prior treatments was 4 (range 1–11); 59% of patients were chemotherapy-resistant. Histology included follicular grade 1–2 (26), grade 3 (2), other indolent (2), and transformed (10). After 2 years on study or after disease progression, long term follow-up was conducted every 6 months for 10 years with CT and laboratory studies. This report presents an update, with investigator-assessed tumor evaluation, from the J Clin Oncol 23:712, 2005.

The median duration of follow-up from the dosimetric dose was 54 (range 1–119) months. The overall response rate was 72% (28 of 39 evaluable patients with 9 complete responders). The median duration of overall response was 18.9 months; the proportion of patients maintaining response at 5 years is estimated at 40% with just two known relapses after two years. Five of 9 complete responders have been continuously maintained. For all 40 study patients, the median progression-free survival (PFS) was 10.4 months (95% CI: 5.7, 18.6) and the estimated 5 year PFS is 28%. The estimated median overall survival for all patients is 80.0 months. To date, 20 deaths have been reported, 10 without documented disease progression. Six second cancers have occurred: 2 acute leukemia, 1 prostate, 2 skin (1 squamous, 1 Merkel cell) and 1 primary hepatic. The incidence of secondary leukemia remains the same as previously reported in 2005 at 5% (2 of 40 patients). Seven of the 40 patients enrolled in this study had elevated thyroid stimulating hormone (TSH) levels prior to receiving the therapeutic dose of iodine-131 tositumomab and 2 patients did not have baseline TSH data. Of the 31 patients with normal baseline TSH levels prior to treatment, 3 developed elevated TSH as of July 2009 and as reported previously (J Clin Oncol 23:712, 2005). There were no cases of hypothyroidism reported as an adverse event by investigators as of July 2009.

The group of extensively pretreated (median = 4) patients participating in this phase II study survived a median of 6.7 years after receiving the BEXXAR® therapeutic regimen. No additional cases of leukemia were seen and no unexpected toxicities were observed. Of the 72% of patients responding to treatment, about 40% were estimated to continue their response at 5 years, including 5 of 9 complete responders. These data demonstrate durable efficacy of BEXXAR® in an indolent lymphoma population with disease progression after rituximab.

Horning:GlaxoSmithKline: Honoraria, Research Funding. Podoloff:GE Healthcare: Honoraria, Research Funding. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Vleisides:GlaxoSmithKline: Employment.