Phase IB Study of Oral Selinexor in Combination with Rituximab and Platinum Chemotherapy in Patients with Relapsed/Refractory B-Cell Lymphoma-Final Analysis.

Autor: Maerevoet M; Hopital Universitaire de Bruxelles, Institut Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium., Casasnovas O; Central Hospital University (CHU) Dijon Bourgogne, 21000 Dijon, France., Cartron G; Central Hospital University (CHU) Montpellier, Hôpital Saint Eloi, 34295 Montpellier, France., Morschhauser F; Centre Hospitalier Régional University (CHRU) de Lille, Hôpital Claude Huriez, 59000 Lille, France., Thieblemont C; Hôpital Saint Louis AP-HP, 75010 Paris, France., Bouabdallah K; Hematology and Cell Therapy Department, University Hospital of Bordeaux, 33000 Bordeaux, France., Feugier P; Centre Hospitalier Régional University (CHRU) Nancy, 54511 Vandœuvre-lès-Nancy, France., Szablewski V; Centre Hospitalier Régional University (CHRU) de Lille, Hôpital Claude Huriez, 59000 Lille, France., Becker S; Nuclear Medicine Department and QuantiF-LITIS Laboratory (EA 4108-FR CNRS 3638), Centre Henri Becquerel, 76038 Rouen, France., Tilly H; Hematology Department and U1245, Centre Henri Becquerel, 76038 Rouen, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Jul 26; Vol. 16 (15). Date of Electronic Publication: 2024 Jul 26.
DOI: 10.3390/cancers16152672
Abstrakt: Purpose: Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma.
Patients and Methods: We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy.
Results: A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3-4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months.
Conclusions: Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile.
Databáze: MEDLINE
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