Introduction: In 2001, we reported results of a pivotal study using BEXXAR in 60 patients (pts) with chemotherapy-refractory NHL who had been previously treated with a minimum of 2 protocol-specified chemotherapy regimens and had either not responded (72%) or had progressed within 6 mos of their last regimen (28%) (

). Enrollment occurred between Nov 1996 and Mar 1998, with a data cutoff for the initial report of 31 Jan 2001. Thirty-six pts had low-grade (LG) NHL, 23 pts had transformed LG NHL, and 1 pt had mantle cell NHL. The median number of prior chemotherapies was 4 (range, 2–13). The overall response rate was 65%. Twelve (20%) of 60 pts achieved a CR; median duration of CR was not reached with 47 mos’ follow-up. At the initial data cutoff, an independent review panel verified that 9 (75%) of 12 CR pts had ongoing responses, without further therapy, ranging from 2.7–4.0 yrs.

Methods: These 9 pts continue to be followed annually for investigator-assessed response. In addition, all 25 pts alive at the time of the last report continue to be followed for long-term safety (hypothyroidism, secondary cancers) for 10 yrs or until death. With a data cut-off of 1 Mar 2004, the minimum follow-up is now 5 yrs.

Results: Of the 9 pts, 3 were >60 yrs of age, 5 had no response to their last chemotherapy; 3 had transformed to a higher histology, 2 had an IPI score ≥3; 4 had BM involvement; 2 had elevated LDH, and 6 had tumors ≥5 cm in diameter. Of the 9 ongoing responders, 7 are still being followed for efficacy and safety. One pt relapsed at 6.9 yrs and continues to be followed for safety. One pt was noncompliant with clinical assessments and was withdrawn from study at 5.0 yrs (still in CR at last follow-up). The remaining 7 pts (~60% of complete responders) remain in continuous CR from 5.0–7.2 yrs. With an additional 37 mos’ follow-up, none of the 25 pts developed an elevated TSH level. The rate of hypothyroidism remains at 4.2%. Six pts developed 8 secondary malignancies (7 skin cancers, 1 GI carcinoma). With 3 yrs’ longer follow-up, no additional cases of MDS have been reported. The annualized incidence of MDS is 2.4%/yr.

Conclusions: In this pivotal study of BEXXAR, durable remissions of ≥5 yrs were achieved following only 1 wk of therapy in 9 heavily pretreated patients with LG, follicular, or transformed NHL who had many poor prognostic features for their disease. With 3 more yrs’ follow-up, long-term safety data remain basically unchanged, with no further reported cases of hypothyroidism or MDS.

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