Treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): focus on the use of tagraxofusp and clinical considerations

Figures & data

Figure 1. Structure and mechanism of action of tagraxofusp. ADP, adenosine diphosphate; IL-3, interleukin-3; IL-3R, IL-3 receptor. Reproduced under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) from Alkharabsheh O, Frankel AE. Clinical Activity and Tolerability of SL-401 (Tagraxofusp): Recombinant Diphtheria Toxin and Interleukin-3 in Hematologic Malignancies. Biomedicines. 2019;7:6. [21] Minor changes (e.g. color) were made.

Table 1. Recommendations for recognizing and managing CLS.

Category	Recommendation
General	For management of CLS specifically, it is critical that patients and the interdisciplinary team receive extensive education for early recognition Of note, there is no absolute definition or definite treatment for CLS, and presentation can vary from patient to patient Closely follow the package label – pay special attention to baseline albumin, creatinine, liver function tests, and daily weights Early treatment is crucial, as CLS can rapidly become fatal, and requires aggressive, team-based interventions
Labs	Laboratory assessments should occur at least daily during treatment, including albumin, ALT, AST, and creatinine Extensive cardiopulmonary assessment should be performed prior to TAG administration (volume status, EF, history of cardiac or pulmonary issues)
TAG dosing	Lead physician approves each dose Dose should be administered midday, when all staff are on duty Therapy should begin on a Monday, if possible
Weight	Weight should be measured daily The same scale should be used daily for an individual patient
Albumin	Early adoption of albumin infusion and measuring drop in albumin to identify CLS is recommended Albumin should be administered once or twice a day when CLS occurs Securing doses of IV albumin before initiating TAG is necessary, as TAG should not be administered if albumin is not available at the center

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CLS, capillary leak syndrome; EF, ejection fraction; IV, intravenous; TAG, tagraxofusp.

Table 2. Recommended TAG dosage modifications [41].

Parameter	Severity Criteria	Dosage Modification
Body weight	≥1.5 kg over pretreatment body weight on prior treatment day	Interrupt TAG dosing until the relevant CLS sign/symptom has resolved
Body temperature	≥38 °C	Withhold TAG until body temperature is <38 °C
Serum creatinine	>1.8 mg/dL (159 micromol/L) or creatinine clearance <60 mL/minute	Withhold TAG until serum creatinine resolves to ≤1.8 mg/dL (159 micromol/L) or creatinine clearance ≥60 mL/minute
Serum albumin	<3.5 g/dL or reduced ≥0.5 g/dL from value measured before initiation of the current cycle	Interrupt TAG dosing until the relevant CLS sign/symptom has resolved
AST or ALT	Increased >5 times the upper limit of normal	Withhold TAG until transaminase elevations are ≤2.5 times the upper limit of normal
Systolic blood pressure	≥160 mmHg or ≤80 mmHg	Withhold TAG until systolic blood pressure is <160 mmHg or >80 mmHg
Heart rate	≥130 bpm or ≤40 bpm	Withhold TAG until heart rate is <130bpm or >40bpm
Hypersensitivity reactions	Mild or moderate	Withhold TAG until resolution of any mild or moderate hypersensitivity reaction. Resume TAG at the same infusion rate
	Severe or life-threatening	Discontinue TAG permanently

ALT, alanine aminotransferase; AST, aspartate aminotransferase; bpm, beats per minute; CLS, capillary leak syndrome; TAG, tagraxofusp.

Alkharabsheh O, Frankel AE. Clinical activity and tolerability of SL-401 (tagraxofusp): recombinant diphtheria toxin and interleukin-3 in hematologic malignancies. Biomedicines. 2019;7(1):6. doi:10.3390/biomedicines7010006

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