Dosimetry results suggest feasibility of radioimmunotherapy using anti-CD138 (B-B4) antibody in multiple myeloma patients

Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on tumor cells in multiple myeloma (MM). This surface antigen is an attractive candidate for targeted therapy, especially radioimmunotherapy (RAIT). We report preliminary biodistribution and dosimetry results obtained in refractory MM patients in a phase I/II RAIT study using iodine-131-labeled anti-CD138 (B-B4) monoclonal antibody (mAb). Four patients with progressive disease were enrolled after three lines of therapy. They received 370 MBq (20 mg/m(2)) of I-131-B-B4 for the dosimetry study. Each patient underwent a whole body (WB) CT and four WB emission scans at days D0, D1, and D3-4. Images were corrected for attenuation and scatter to assess doses absorbed by organs and bone marrow (BM). Blood and urine samples were additionally collected. Dosimetry was conducted using the MIRD method. Images obtained 1 h after I-131-B-B4 injection showed high BM and liver uptake without kidney uptake. The BM uptake confirmed BM involvement as detected by pre-inclusion FDG PET/CT. Absorbed doses were calculated at 2.03 +/- 0.3 mGy/MBq for the liver, 1.10 +/- 0.9 mGy/MBq for the kidneys, and 0.52 +/- 0.20 mGy/MBq for the BM. Grade III thrombocytopenia was documented in two cases (highest BM-absorbed doses), and no grade IV hematological toxicity was observed. Therefore, autologous stem cells were not infused. One patient out of four experienced partial response, with 60% reduction of M-spike on serum electrophoresis, and total relief of pain, lasting for 1 year. This patient was able to go back to work. In this proof of concept study based on dosimetry, we show that MM RAIT is feasible using the anti-CD138 antibody. It would be of great interest to perform a RAIT phase I/II trial with a humanized anti-CD138 mAb with increased doses and systematic autologous stem cell infusions to overcome hematological toxicity and achieve efficacy.