ANCHOR : melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study
Ocio, Enrique M. (Instituto de Investigación Sanitaria Valdecilla (Santander, Cantàbria))
Efebera, Yvonne A. (OhioHealth (Estats Units d'Amèrica))
Hájek, Roman (University Hospital Ostrava (República Txeca))
Straub, Jan (Všeobecná Fakultní Nemocnice (Praga, República Txeca))
Maisnar, Vladimir (Charles University Hospital (Hradec Králové, República Txeca))
Eveillard, Jean-Richard (Hôpital Morvan (Brest, República Txeca))
Karlin, Lionel (University Claude Bernard Lyon 1 (França))
Mateos, M. V (Instituto de Investigación Biomédica de Salamanca)
Oriol, Albert (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribrag, Vicent (Université Paris-Saclay)
Richardson, Paul G. (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica))
Norin, Stefan (Oncopeptides (Estocolm, Holanda))
Obermüller, Jakob (Oncopeptides (Estocolm, Holanda))
Bakker, Nicolaas A. (Oncopeptides (Estocolm, Holanda))
Pour, Luděk (Fakultní Nemocnice (Brno, República Txeca))

Data:	2024
Resum:	Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1. 3 mg/m; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor and who had received one to four prior lines of therapy. Primary objectives were to determine the optimal dose of melflufen in triplet combination (phase I) and overall response rate (phase IIa). In total, 33 patients were treated in the daratumumab arm and 23 patients received therapy in the bortezomib arm. No dose-limiting toxicities were reported at either melflufen dose level with either combination. With both triplet regimens, the most common grade ≥3 treatment-emergent adverse events were thrombocytopenia and neutropenia; thrombocytopenia was the most common treatment-emergent adverse event leading to treatment discontinuation. In the daratumumab arm, patients receiving melflufen 30 mg remained on treatment longer than those receiving the 40-mg dose. In the daratumumab arm, the overall response rate was 73% and median progression-free survival was 12. 9 months. Notably, in the bortezomib arm, the overall response rate was 78% and median progression-free survival was 14. 7 months. Considering the totality of the data, melflufen 30 mg was established as the recommended dose for use with dexamethasone and daratumumab or bortezomib for future studies in relapsed/refractory MM.
Nota:	Funding for the study (ClinicalTrials.gov identifier: NCT04649060) and for editorial assistance was provided by Oncopeptides AB.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antibodies, Monoclonal ; Bortezomib ; Dexamethasone ; Humans ; Melphalan ; Multiple Myeloma ; Neoplasms, Plasma Cell ; Neutropenia ; Phenylalanine ; Thrombocytopenia
Publicat a:	Haematologica, Vol. 109 Núm. 3 (march 2024) , p. 867-876, ISSN 1592-8721

DOI: 10.3324/haematol.2023.283490
PMID: 37646657

10 p, 1.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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