Cusatuzumab for treatment of CD70-positive relapsed or refractory cutaneous T-cell lymphoma.

Autor: Leupin N; Argenx, Zwijnaarde, Belgium., Zinzani PL; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Istituto di Ematologia 'Seràgnoli,' Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università degli Studi, Bologna, Italy., Morschhauser F; Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Université de Lille, CHU Lille, EA 7365, Lille, France., Dalle S; Department of Dermatology, Centre Hospitalier Lyon Sud, Pierre Bénite, France., Maerevoet M; Service Hématologie, Institut Jules Bordet, Brussels, Belgium., Michot JM; Gustave Roussy, Villejuif, France., Ribrag V; Gustave Roussy, Villejuif, France., Offner F; University Hospital Gent, Gent, Belgium., Beylot-Barry M; Inserm U1053, Department of Dermatology, Centre Hospitalier, Bordeaux, France., Moins-Teisserenc H; Hôpital Saint Louis, Université de Paris, INSERM U1160, Paris, France., Zwaenepoel K; Department of Pathology, University Hospital Antwerp, Edegem, Belgium., de Winne K; Department of Pathology, University Hospital Antwerp, Edegem, Belgium., Battistella M; Hôpital Saint Louis, Université de Paris, INSERM U1160, Paris, France., Hultberg A; Argenx, Zwijnaarde, Belgium., Gandini D; Argenx, Zwijnaarde, Belgium., Moshir M; Argenx, Zwijnaarde, Belgium., Jacobs J; Argenx, Zwijnaarde, Belgium., Delahaye T; Argenx, Zwijnaarde, Belgium., Khan A; Argenx, Zwijnaarde, Belgium., Zabrocki P; Argenx, Zwijnaarde, Belgium., Silence K; Argenx, Zwijnaarde, Belgium., van Rompaey L; Argenx, Zwijnaarde, Belgium., Borg C; Inserm U645, Centre Hospitalier Universitaire de Besançon, Besançon, France., Motta G; Division of Hematopathology, European Institute of Oncology, IRCCS, Milan, Italy., Melle F; Division of Hematopathology, European Institute of Oncology, IRCCS, Milan, Italy., Calleri A; Division of Hematopathology, European Institute of Oncology, IRCCS, Milan, Italy., Pauwels P; Department of Pathology, University Hospital Antwerp, Edegem, Belgium., de Haard H; Argenx, Zwijnaarde, Belgium., Pileri S; Division of Hematopathology, European Institute of Oncology, IRCCS, Milan, Italy., Bagot M; Inserm U976, Hôpital Saint Louis, Université de Paris, Paris, France.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2022 Mar 01; Vol. 128 (5), pp. 1004-1014. Date of Electronic Publication: 2021 Nov 02.
DOI: 10.1002/cncr.34005
Abstrakt: Background: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).
Methods: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed.
Results: The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses.
Conclusions: Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development.
(© 2021 American Cancer Society.)
Databáze: MEDLINE
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