Figure 4.
Laboratory course of patient 004. At treatment initiation, patient 004 had a hemoglobin level of 7.4 g/dL. She was started on 45 mg/kg (3.4 g) sutimlimab which rapidly abrogated hemolysis and increased her hemoglobin level by 5.8 g/dL over the course of 4 weeks. Patient 004 experienced laboratory evidence of breakthrough hemolysis after the sixth and seventh doses of sutimlimab. However, when blood sampling was performed 1 week after the seventh dose of sutimlimab, the hemoglobin level was slightly increased and the bilirubin level normalized, suggesting that the treatment effect of sutimlimab was sufficient for at least 7 days but not sufficient for an interval of 14 days. This indicates that either the dose needed to be increased or the dosing interval needed to be decreased to achieve a sustained treatment effect. Despite underdosing, patient 004 was deliberately continued on 45 mg/kg of sutimlimab to allow for the detection of a putative beneficial effect of concomitantly started treatment with rituximab. The patient was eventually switched to a 5.5-g fixed-dose regimen, resulting in a rapid increase of hemoglobin and a decrease of bilirubin. Patient 004 experienced a washout of sutimlimab after the second fixed dose and her hemoglobin dropped to 9.2 g/dL. However, after 2 infusion cycles of sutimlimab, her hemoglobin promptly increased again to a level of 11.5 g/dL. During a scheduled checkup 2 weeks later, her hemoglobin level had further increased by 2.2 g/dL to a peak level of 13.7 g/dL, concluding the NPP. The investigator decided to discontinue treating this patient because she had repeated falls as a result of unrelated hydrocephalus, which required a shunt operation. In spite of a fifth dose of rituximab administered after the NPP, patient 004 could not maintain normal hemoglobin levels. Her hemoglobin levels decreased by more than 4 g/dL within 3 weeks to a level of 9.5 g/dL and then ranged from 7.7 to 10.2 g/dL over the following months, eventually reaching a nadir of 7.3 g/dL 8 months later.

Laboratory course of patient 004. At treatment initiation, patient 004 had a hemoglobin level of 7.4 g/dL. She was started on 45 mg/kg (3.4 g) sutimlimab which rapidly abrogated hemolysis and increased her hemoglobin level by 5.8 g/dL over the course of 4 weeks. Patient 004 experienced laboratory evidence of breakthrough hemolysis after the sixth and seventh doses of sutimlimab. However, when blood sampling was performed 1 week after the seventh dose of sutimlimab, the hemoglobin level was slightly increased and the bilirubin level normalized, suggesting that the treatment effect of sutimlimab was sufficient for at least 7 days but not sufficient for an interval of 14 days. This indicates that either the dose needed to be increased or the dosing interval needed to be decreased to achieve a sustained treatment effect. Despite underdosing, patient 004 was deliberately continued on 45 mg/kg of sutimlimab to allow for the detection of a putative beneficial effect of concomitantly started treatment with rituximab. The patient was eventually switched to a 5.5-g fixed-dose regimen, resulting in a rapid increase of hemoglobin and a decrease of bilirubin. Patient 004 experienced a washout of sutimlimab after the second fixed dose and her hemoglobin dropped to 9.2 g/dL. However, after 2 infusion cycles of sutimlimab, her hemoglobin promptly increased again to a level of 11.5 g/dL. During a scheduled checkup 2 weeks later, her hemoglobin level had further increased by 2.2 g/dL to a peak level of 13.7 g/dL, concluding the NPP. The investigator decided to discontinue treating this patient because she had repeated falls as a result of unrelated hydrocephalus, which required a shunt operation. In spite of a fifth dose of rituximab administered after the NPP, patient 004 could not maintain normal hemoglobin levels. Her hemoglobin levels decreased by more than 4 g/dL within 3 weeks to a level of 9.5 g/dL and then ranged from 7.7 to 10.2 g/dL over the following months, eventually reaching a nadir of 7.3 g/dL 8 months later.

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