Effect of antilymphoma antibody, ¹³¹I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma

Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan®, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled ⁹⁰Y-ibritumomab (Zevalin®, Biogen Idec Inc., Cambridge, MA) and ¹³¹I-tositumomab (Bexxar®; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 ( ¹³¹I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received ¹³¹I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last ¹³¹I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last ¹³¹I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or ¹³¹1 dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of ¹³¹I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after ¹³¹I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.