Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma with a high rate of disease relapse despite the achievement of clinical responses to frontline chemoimmunotherapy treatments. Loncastuximab tesirine-lpyl is a novel anti-CD19 antibody conjugated to an alkylating pyrrolobenzodiazepine agent (SG3199), and it has been approved for relapsed/refractory (r/r) DLBCL. Baseline moderate to severe hepatic impairment has an unclear impact on the safety of loncastuximab tesirine-lpyl, and there is a lack of clear guidance on dose adjustment from the manufacturer. The authors present two cases of r/r DLBCL safely treated with full-dose loncastuximab tesirine-lpyl in the setting of severe hepatic dysfunction.     

Single-dose rasburicase for tumour lysis syndrome in adults: weight-based approach

Background: The optimal rasburicase dose for adult patients has not been determined. Objective: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. Method: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome‐associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. Result: Twenty‐one patients received rasburicase with an average first dose of 0·15 ± 0·03 mg/kg. The drug dosing was calculated based on the patients’ ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89·7 ± 9·0% from the baseline through the first 24 h after a single rasburicase dose (11·4 ± 4·5 mg/dL vs. 1·4 ± 1·4 mg/dL, respectively, P < 0·001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer’s recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24–72 h after the single rasburicase dose were not significantly different from baseline (1·8 mg/dL vs. 2·3 mg/dL, respectively, P = 0·14). Conclusion: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia‐associated nephrotoxicity. From our experience, a single dose of 0·15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h.