Topics:

Fludarabine Monophosphate Followed by Iodine-131 Tositumomab Fludarabine Monophosphate Followed by Iodine-131 Tositumomab (NHL)

Fludarabine Monophosphate Followed by Iodine-131 Tositumomab Fludarabine Monophosphate Followed by Iodine-131 Tositumomab (NHL)

Iodine-131 tositumomab (Bexxar), a radiolabeled immunoglobulin G2a (IgG2a) monoclonal antibody directed against the CD20 antigen, is effective in the treatment of previously untreated, as well as relapsed and refractory, low-grade and transformed, low-grade non-Hodgkin’s lymphoma (NHL). Fludarabine (Fludara) is also active as a single agent or in combination in NHL. In vitro data have shown that iodine-131 tositumomab and fludarabine have a markedly supraadditive effect on tumor cell killing.

We are evaluating the safety and efficacy of a sequential regimen of three cycles of fludarabine (25 mg/m² × 5 d q5wk) followed, 6 to 8 weeks later, by tositumomab and iodine-131 tositumomab for patients with previously untreated, low-grade, transformed, low-grade or follicular NHL. A total of 38 patients were enrolled, 14 of whom are evaluable for response at least 3 months post-treatment with iodine-131 tositumomab. Baseline patient characteristics (N = 14) were: median age, 52.5 years, > 60 years old (2 patients), male (7 patients), median time from diagnosis (2 months), and stage at time of treatment (stage II, 1 patient; stage IV, 13 patients).

Patients received a single dosimetric dose (450 mg of tositumomab intravenously [IV] followed by 35 mg [5 mCi] of iodine-131 tositumomab over 20 minutes) and then had three whole-body counts obtained over the next 7 days. The whole body counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose

(65 cGy for platelet counts of 100,000 to 149,000 cells/mm³ and 75 cGy for platelets ³ 150,000 cells/mm³). The single therapeutic dose (450 mg of tositumomab IV followed by 35 mg of tositumomab containing an appropriate amount of activity [mCi] of iodine-131 to deliver the specified total-body dose [cGy] over 20 minutes) was administered 7 to 14 days after the dosimetric dose.

The toxicity following fludarabine was mainly hematologic. The principal toxicity following iodine-131 tositumomab was also hematologic: absolute neutrophil count (ANC) was < 500 cells/mm³ in five patients (36%); platelet count was < 10,000 cells/mm³ in one patient (7%). Nonhematologic toxicity was typically mild to moderate; the most frequent events were nausea, asthenia, headache, increased cough, and rhinitis. One patient developed antimurine antibodies (HAMA).

An investigator-assessed response was seen in 13 of 14 patients (93%; 2 complete responses [CRs], 11 partial responses [PRs]) after fludarabine. At 25 weeks after treatment with iodine-131 tositumomab, 14 (100%) of 14 patients had achieved a response (10 CRs [71%], 4 PRs). Of the 11 PRs after fludarabine, 7 converted to CRs after iodine-131 tositumomab. One patient with stable disease after fludarabine converted to a CR. Three patients have developed progressive disease. Only one patient required a reduction in the fludarabine dosage.

CONCLUSIONS: Fludarabine, followed by tositumomab and iodine-131 tositumomab, can be safely administered to patients. The immunosuppressive effects of fludarabine limit the seroconversion to HAMA positivity in patients receiving tositumomab and iodine-131 tositumomab. The efficacy of tositumomab and iodine-131 tositumomab appears to augment that of fludarabine, improving overall responses and CRs. All treated and evaluated patients exhibited a response during the study. Additional patients have been treated and will be assessed.

Click here for Dr. Bruce Cheson’s commentary on this abstract.

 
Loading comments...
Please Wait 20 seconds or click here to close