CONTINUOUS-INFUSION OF THE ANTI-CD22 IMMUNOTOXIN IGG-RFB4-SMPT-DGA INPATIENTS WITH B-CELL LYMPHOMA - A PHASE-I STUDY

IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupl ed to the monoclonal antihuman CD22 antibody, RFB4. This study determi ned the maximally tolerated dose (MTD) of this immunotoxin (IT) admini stered as a continuous 8-day infusion to 18 patients with B-cell lymph oma (30% CD22(+) tumor cells) over 8 days. The MTD was 19.2 mg/m(2)/19 2 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as d ose-limiting toxicity (DLT) at 28.8 mg/m(2)/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT conce ntrations greater than 1,000 ng/mL and the absence of circulating tumo r cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial r esponses, 3 minor responses, 6 stable disease, and 3 progression of di sease were observed. The mean maximal serum concentration (C-max) in i nitial courses at the MTD (19.2 mg/m(2)) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m(2)/192 h, the C-max was highly varia ble (n =11 mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human anti mouse or antiricin antibodies developed in 6 of 16 (37.5%) patients af ter one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did n ot correlate with toxicity but decreased soluble interleukin-2 recepto r concentrations correlated with clinical response. Comparison to a pr ior study with the same It administered by intermittent bolus infusion s (Amlot et al, Blood 82:2624, 1993) suggests similar clinical respons e, toxicity, and immunogenicity. This is a US government work. There a re no restrictions on its use.