Page 205 - Haematologica Vol. 109 - July 2024

ARTICLE - Plasma Cell Disorders
Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, non- randomized, multicenter GEM-SELIBORDARA study
Verónica González-Calle,1* Paula Rodríguez-Otero,2* Anna Sureda,3 Felipe de Arriba,4 Marta Reinoso,5 Paz Ribas,6 Ana Pilar González-Rodríguez,7 Yolanda González,8 Albert Oriol,9 Joaquín Martínez-López,10 Marta Sonia González,11 Miguel T. Hernández,12 Maialen Sirvent,13 Teresa Cedena,10 Noemí Puig,1 Bruno Paiva,2 Joan Bladé,14 Juan José Lahuerta,10 Jesús F. San-Miguel2 and María-Victoria Mateos1
1Department of Hematology, University Hospital of Salamanca, CAUSA, IBSAL and Center for Biomedical Research in Network of Cancer, CIBERONC, Salamanca; 2Cancer Center Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona; 3Serve d’Hematologia Clínica, Institut Català D’Oncologia-L’Hospitalet. IDIBELL, Universitat de Barcelona, Barcelona; 4Hospital Morales Meseguer, IMIB-Pascual Parrilla, Universidad de Murcia, Murcia; 5Hospital Universitario Virgen del Rocío, Sevilla; 6Hospital Universitario Dr. Peset, Valencia; 7Hospital Universitario Central de Asturias, Oviedo; 8Institut Catalá D’Oncologia Girona, Girona; 9Institut Catalá D’Oncologia Badalona, Badalona; 10Hospital Universitario 12 de Octubre, Madrid; 11Complejo Hospitalario Universitario de Santiago, La Coruña; 12Hospital Universitario de Canarias, Tenerife; 13Hospital Donostia, San Sebastián and 14Hospital Clinic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain
*VG-C and PR-O contributed equally as first authors.
Abstract
The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinex- or, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexa- methasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd).
A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least three prior lines (PL) of therapy and part 2 enrolled an early relapse population with at least one PL of therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of three PL. Overall response rate (ORR) was 50% with two CR. Median progres- sion-free survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of one PL. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide-refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent non-hematological adverse event (38%; grade 3-4: 6%). Sixty-two percent of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.
Haematologica | 109 July 2024
Correspondence: P. Rodriguez-Otero paurodriguez@unav.es
Received: Accepted: Early view:
September 20, 2023. February 2, 2024. February 15, 2024.
https://doi.org/10.3324/haematol.2023.284089
©2024 Ferrata Storti Foundation Published under a CC BY-NC license
2219