Low- versus high-dose radioimmunotherapy with humanized anti-CD22 or chimeric anti-CD20 antibodies in a broad spectrum of B cell-associated malignancies

Both CD22 and CD20 have been used successfully as target molecules for radi oimmunotherapy (RAIT) of low-grade B cell non-Hodgkin's lymphoma. Because b oth CD20 and CD22 are highly expressed relatively early in the course of B cell maturation, and because its expression is maintained up to relatively mature stages, we studied the potential of the humanized anti-CD22 antibody , hLL2, as well as of the chimeric anti-CD20 (chCD20) antibody, rituximab ( IDEC-C2B8), for low- or high-dose (myeloablative) BAIT of a broad range of B cell-associated hematological malignancies. A total of 10 patients with chemorefractory malignant neoplasms of B cell o rigin were studied with diagnostic (n = 5) and/or potentially therapeutic d oses (n = 9) of hLL2 (n = 4; 0.5 mg/kg, 8-315 mCi of I-131) or chCD20 (n = 5; 2.5 mg/kg, 15-495 mCi of I-131). The diagnostic doses were given to esta blish the patients' eligibility for RAIT and to estimate the individual rad iation dosimetry. One patient suffered of Waldenstrom's macroglobulinemia, eight patients had low-(n = 4), intermediate- (n = 2) or high- (n = 2) grad e non-Hodgkin's lymphoma, and one patient had a chemorefractory acute lymph atic leukemia, after having failed five heterologous bone marrow or stem ce ll transplantations. Three of these 10 patients were scheduled for treatmen t with conventional (30-63 mCi, cumulated doses of up to 90 mCi of I-131) a nd 7 with potentially myeloablative (225-495 mCi of I-131) activities of I- 131-labeled hLL2 or chCD20 (0.5 and 2.5 mg/kg, respectively); homologous (n = 6) or heterologous (n = 1) stem cell support was provided in these cases . Good tumor targeting was observed in all diagnostic as well as posttherapeu tic scans of all patients. In myeloablative therapies, the therapeutic acti vities were calculated based on the diagnostic radiation dosimetry, aiming at lung and kidney doses less than or equal to 20Gy. Stem cells were reinfu sed when the whole-body activity retention fell below 20 mCi. In eight asse ssable patients, five had complete remissions, two experienced partial remi ssions (corresponding to an overall response rate of 87%), and one (low-dos e) patient had progressive disease despite therapy. In the five assessable, actually stem-cell grafted patients, the complete response rate was 100%. Both CD20 and CD22 seem to be suitable target molecules for high-dose RAIT in a broad spectrum of hematological malignancies of B cell origin with a b road range of maturation stages (from acute lymphatic leukemia to Waldenstr om's macroglobulinemia). The better therapeutic outcome of patients undergo ing high-dose, myeloablative RAIT favors this treatment concept over conven tional, low-dose regimens.