High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support

Open Access
Publisher Website
Google Scholar
Abstract
BACKGROUND CD20 has been used successfully as a target molecule for conventional low‐dose, as well as high‐dose, myeloablative radioimmunotherapy (RIT) of B‐cell non‐Hodgkin lymphoma (NHL). Mantle cell lymphoma (MCL) is an especially aggressive, prognostically unfavorable subtype of B‐cell NHL, associated with an overall 5‐year survival rate of less than 20%. Recent evidence has failed to show convincing therapeutic efficacy of conventional, nonmyeloablative RIT in patients with MCL. The aim of this pilot study was to investigate whether high‐dose, myeloablative RIT with the iodine‐131 (131I)–labeled chimeric anti‐CD20 antibody C2B8 (rituximab, obtained as Mabthera from Roche Pharma, Reinach, Switzerland) is therapeutically effective in MCL patients. METHODS A total of seven patients with chemorefractory or relapsed MCL were studied in this pilot trial. All had relapsed after high‐dose chemotherapy with autologous stem cell transplantation (four of them combined with 12 grays (Gy) total‐body irradiation). A diagnostic‐dosimetric study was performed with approximately 10 mCi of 131I‐labeled C2B8 at a protein dose of 2.5 mg per kg body weight, in order to assess its biodistribution and dosimetry. If splenic pooling was observed, as is typically the case in patients with splenomegaly, the protein dose was doubled in additional studies until a “favorable” biodistribution was obtained. Therapy was performed with myeloablative doses of 261–495 mCi of 131I‐labeled C2B8 at the previously optimized protein dose, aiming at lung doses ≤ 27 Gy. Homologous stem cell support was provided. Clinical follow‐up was obtained at 3‐month intervals for up to 38 months (median observation time, 25 months). Overall, in six patients the 2.5 mg/kg protein dose was used, whereas in one patient with splenomegaly, 10 mg/kg was necessary to overcome the splenic antigenic sink. RESULTS Blood cell nadirs were reached at 2–3 weeks after therapy infusion, but all patients reengrafted at 7–10 days after stem cell reinfusion. Nonhematologic toxicity was restricted to mild‐to‐moderate nausea, fever, transient bilirubin, or liver enzyme elevations. One patient with preexisting alcoholic cirrhosis experienced a deterioration of liver function. Despite thyroid blocking, 5 of 7 patients developed hypothyroidism, requiring thyroxine substitution at 6–18 months after RIT. Six patients experienced a complete and one a good partial remission. Five patients were still in CR at the time this article was written, and six are still alive for more than 3 years; one patient relapsed locally at 3 months and one systemically at 26 months after RIT. CONCLUSIONS High‐dose myeloablative radioimmunotherapy with 131I‐labeled anti‐CD20 antibodies seems to be associated with a high response rate and moderate toxicity in patients with MCL. Further follow‐up to monitor the long‐term outcome as well as systematic prospective clinical studies are indicated. Cancer 2002;94:1363–72. © 2002 American Cancer Society. DOI 10.1002/cncr.10307