ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 20

Written in Blood suggest that “elimination of MRD was significantly associated with prolonged CR duration (p<0.0001),” the authors observed. The authors assessed nine patients for lymphocyte subsets before and after treatment: Circulating HCL cells cleared in all patients, but normal B cells decreased by <50 percent in three patients and increased in all others. T cells and their subsets increased in all but one patient, “thus, [the anti-CD22 drug] spared T cells and, with its short half-life, avoided prolonged B-cell depletion,” they noted. “Moxetumomab pasudotox 50 µg/kg, particularly with consolidation cycles, cleared MRD in more than half of [patients who experienced] CR,” the authors wrote, noting that MRD clear- ance was associated with improved CR duration. Of the 29 patients who received the 50 µg/kg dose, 22 (76%) clearing MRD in the blood had higher CR (n=19/22 vs. n=1/7; p=0.001) and higher overall response rates (n=22/22 vs. n=4/7; p=0.01), compared with those who never achieved MRD- negativity. Pharmacokinetics analysis in 29 evaluable patients revealed that plasma concentrations of moxetu- momab increased 213 percent during cycle one (p<0.001) and increased 121 percent during cycle two from days one to five (p=0.002). The volumes of distribution and clear- ances decreased, while soluble CD22 levels and HCL burden decreased, per enzyme-linked immunosorbent assays. These findings, the authors noted, suggest “moxetumomab pasu- dotox at 50 μg/kg achieved cytotoxic plasma levels that increased with rapid resolution of tumor burden and were not completely blocked when neutralizing antibodies were first detectable.” An ongoing multicenter, pivotal study is assessing moxetumomab pasudotox in patients with relapsed/ refractory HCL. This early-phase study is limited by its small patient population and lack of a comparator arm. MedImmune provided support for the study. Some of the authors are co- inventors of immunotoxin patents assigned to the government of the U.S., as represented by the secretary of the Department of Health and Human Services on behalf of the National Institutes of Health, which are licensed by MedImmune. REFERENCE Kreitman RJ, Tallman MS, Robak T, et al. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase I results and long-term follow-up. Blood. 2018 February 27. [Epub a