The use of 166Ho-DOTMP followed by autologous stem cell transplantation (ASCT) has been reported in patients with multiple myeloma (MM). In MM, radiotherapy plays an important role both in ASCT and palliation of bone lesions. Application of bone-seeking radioisotopes has proven effective in treatment of osteolytic lesions. Malignant plasma cells in myeloma are located predominantely in areas of bone resorption. Thus targeting of bone lesions may be a suitable approach in high-dose therapy. When compared to 166Ho-DOTMP, 153 Samarium-EDTMP has some advantages: it is easier accessible in terms of production and logistics; has a longer physical half-life and shows higher skeletal retention. We treated two patients with refractory MM with myeloablative dosages of 153 Samarium-EDTMP up to 60 GBq. Patient 1 relapsed from CR 39 months and patient 2 had symptomatic relapse 9 months, each after one course of high-dose melphalan. Both patients were refractory to 2 salvage chemotherapy regimens. They received 153 Samarium-EDTMP with a bone marrow dose of 28 (patient 1) and 35 Gy respectively. Doses to bone marrow were derived from scan data and the results of blood sampling and urine collection over 48 hours. Melphalan 140 mg/m² was given on days -3 and -2. Hemorrhagic cystitis was successfully prevented by continuous bladder irrigation. They experienced myeloablation already prior to high-dose melphalan and received ASCT 17 (patient 1) and 12 days after application of 153 Samarium-EDTMP respectively. During aplasia, the first patient developed pulmonary infiltrates (possible invasive aspergillosis) and unfortunately died on day +8 due to cerebral hemorrhage. The second patient experienced reversible renal failure and WHO °III liver toxicity. Following neutrophil engraftment on day +13, he recovered completely. The patient achieved partial remission for 6 months. Even though experience with application of 153 Samarium-EDTMP and high-dose melphalan prior to ASCT is limited, we suppose it is an attractive treatment option in MM. The most important advantage of bone-seeking radiopharmaceutics when compared to external beam radiation is optimal lesion specific delivery, thus enabling the application of higher sceletal dosages. Distribution kinetics are required for each given patient to avoid toxicity to kidney, lung and liver. Toxicity of bone-seeking radionuclides is probably higher in extensively pretreated patients especially with regard to renal dysfunction.
Full conference title:
30th Annual Meeting of the European Group for Blood and Marrow Transplantation
- EBMT 2004