Laboratory course of patient 001. To target the underlying lymphoplasmacytic lymphoma, patient 001 had been treated with ibrutinib since her participation in the phase 1B trial. Her initial hemoglobin level was 7.7 g/dL accompanied by distinct laboratory markers of hemolysis. After initiation of ibrutinib, her IgM levels started to decrease, and her bilirubin levels steadily increased. Hemoglobin levels continued to improve until the patient suffered a urinary tract infection, which triggered a hemolytic crisis and caused a sudden drop in hemoglobin level and a peak in bilirubin level. She was subsequently re-treated with sutimlimab 60 mg/kg (3.4 g) on top of antibiotic therapy and responded with normalization of bilirubin within 3 days, a 1.6 g/dL increase in hemoglobin within 6 days, and a complete normalization of anemia within 5 weeks. The patient’s haptoglobin levels remained below measurable limits, indicating fully compensated residual hemolysis. *In week 9, the patient presented with increased levels of bilirubin (1.49 mg/dL) and LDH (566 U/L), while still retaining a normal level of hemoglobin, which we therefore classified as early breakthrough hemolysis.