Public Release: 

New radioimmunotherapy cancer treatment

Society of Nuclear Medicine

A major advance in cancer therapy--high dose radioimmunotherapy--resulted in long-term remission for persons with mantle cell lymphoma. This often-fatal form of Non-Hodgkin's Lymphoma (NHL) has a mean survival time of only 36-60 months from original diagnosis.

In a study being highlighted at the Society of Nuclear Medicine 49th Annual Meeting in Los Angeles, researchers from Germany studied twelve patients who had already relapsed after high-dose chemotherapy. Their study compared low-dose rituxan-based radioimmunotherapy (RIT) with a high-dose regimen of the same therapy. Seven of eight patients who received the high-dose RIT had a complete remission, compared to only one of four with low dose. The remaining high-dose person had a partial remission. At the time of publication, six of the eight (75%) were still in complete remission, and seven of the eight--or 87% of the high-dose patients--were still living after 42 months.

RIT is one of the most promising of a new class of cancer-fighting therapies. It combines the power of nuclear medicine radiation therapy with the targeting capacity of monoclonal antibodies that target specific cancer cells, often without the major side effects of conventional chemotherapy. The significantly improved survival without major side effects of the higher-dose RIT is considered particularly important, even though the study itself was relatively small.

The patients received either 30-75 mCi (low dose) or 261-515 mCi (high dose) of 131I-C2B8. 131I-C2B8 is a monoclonal antibody (rituxan) to which, 131I, a well known, iodine-based radiopharmaceutical used in radiation therapy, has been attached. Side effects were moderate in the patients receiving the high-dose therapy and included mild to moderate nausea, fever and transient bilirubin (bile level) or liver enzyme elevations. A number of patientdeveloped hypothyroidism and required thyroid treatment. The German study received the highest possible score by the SNM annual meeting review panel, which selects papers for presentation based on scientific merit and technical quality.

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Approximately 53,900 persons in the US contract Non-Hodgin's Lymphoma every year, and of these 5% have mantle cell-lymphoma, which is considered to be a particularly aggressive form of the disease with a poor prognosis.

HIGH-DOSE MYELOABLATIVE VERSUS CONVENTIONAL LOW-DOSE RADIOIMMUNOTHERAPY (RIT) OF MANTLE CELL LYMPHOMA (MCL) WITH THE CHIMERIC ANTI-CD20 ANTIBODY C2B8. was authored by T. M. Behr*, M. Gotthardt, M. L. Schipper, S. Gratz, G. Brittinger, B. Wörmann, W. Becker, M. P. Béhé, Department of Nuclear Medicine, Philipps-University of Marburg, Marburg, Germany; Department of Hematology/Oncology of the Georg-August-University, Göttingen, Germany; Department of Nuclear Medicine of the Georg-August-University, Göttingen, Germany. (200614).

The Society of Nuclear Medicine Annual Meeting is being held June 15-19 at the Los Angeles Convention Center, Los Angeles, CA. In addition to educational sessions, the meeting will focus on leading medical developments in the field of nuclear medicine including radioimmunotherapies, which are a new class of drugs fighting cancer, diagnostic breakthroughs with Positron Emission Tomography (PET) and other topics. More than 5,000 specialists in the field of nuclear medicine--including scientists, technologists, researchers and the medical industry industry-are expected to attend. The Society of Nuclear Medicine is an international scientific and professional organization of more than 13,000 members dedicated to promoting the science, technology and practical applications of nuclear medicine. The SNM is based in Reston, VA.

For late-breaking news about the world of nuclear medicine and events at the 49th Annual Society of Nuclear Medicine meeting, visit www.snm.org

Society of Nuclear Medicine
Annual Meeting Abstract # 414
HIGH-DOSE MYELOABLATIVE VERSUS CONVENTIONAL LOW-DOSE RADIOIMMUNOTHERAPY (RIT) OF MANTLE CELL LYMPHOMA (MCL) WITH THE CHIMERIC ANTI-CD20 ANTIBODY
C2B8.T. M. Behr*, M. Gotthardt, M. L. Schipper, S. Gratz, G. Brittinger, B. Wörmann, W. Becker, M. P. Béhé, Department of Nuclear Medicine, Philipps-University of Marburg, Marburg, Germany; Philipps-University of Marburg, Marburg, Germany; Department of Hematology/Oncology of the Georg-August-University, Göttingen, Germany; Department of Nuclear Medicine of the Georg-August-University, Göttingen, Germany. (200614) Objectives: CD20 has been used as target molecule for low-dose as well as high-dose, myeloablative RIT of B-cell NHL. MCL is an especially aggressive, prognostically unfavorable form of B-cell NHL. The aim of this study was to investigate whether high-dose, myeloablative RIT with the 131I-labeled chimeric anti-CD20 antibody C2B8 (rituxan, Mabthera®, Roche) may be therapeutically more effective in MCL. Methods: A total of twelve patients with chemorefractory or relapsed mantle cell lymphoma were studied so far (all of them having relapsed after high-dose chemotherapy, seven of them combined with 12 Gy TBI). A diagnostic-dosimetric study was performed with 10 mCi of 131I-C2B8 at a protein dose of 2.5 mg/kg. In case of splenic pooling, the protein dose was increased until a more "favorable" biodistribution was obtained. Therapy was performed with conventional (30-75 mCi; n=4) or myeloablative activties (261-515 mCi; n=8) of 131I-C2B8 at the previously optimized protein dose, aiming at whole-body doses of £ 0.8 Gy (for low-dose RIT) or lung doses of £ 27 Gy (for high-dose RIT). Clinical follow-up was obtained for up to 42 months. Results: Overall, in 11 patients the 2.5 mg/kg protein dose was used, whereas in one patient with marked splenomegaly, 10 mg/kg were necessary to overcome the splenic antigenic sink. In the high-dose patients, non-hematologic toxicity was restricted to mild to moderate nausea, fever, transient bilirubine or liver enzyme elevations. Despite thyroid blocking, 6/8 high-dose (in contrast to 0/4 low-dose) patients developed hypothyroidism, requiring thyroxine substitution at 6-18 months after RIT. The response rate in the low-dose arm was only 1(PR)/4, whereas 7/8 high-dose patients experienced complete and the remainder a partial remission. 6 high-dose patients are still in CR (one of them relapsed locally at 3 months, one systemically at 26 months after RIT), and 7 are still alive for up to 42+ months. Conclusions: In contrast to low-dose therapy, high-dose RIT with 131I-labeled anti-CD20 antibodies seems to be associated with a high response rate at moderate toxicity in patients with MCL.

Session Title: Oncology - Therapy: Radioimmunotherapy - LymphomaSession Type: Scientific Paper Session Date: Tuesday, June 18No. 4149:45 AM - 11:15 a.m. Room 4006AB

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