Simple Summary Diffuse large B-cell lymphoma (DLBCL) is a complex disease. A combination of immunotherapy and chemotherapy is used to treat DLBCL at initial diagnosis. Additional treatments are available when DLBCL does not respond to initial treatment; however, for many patients, DLBCL will stop responding to treatment (relapse) or may not respond at all (refractory). Selinexor is a novel, oral medication that belongs to a class of drugs called selective inhibitors of nuclear export, and it works by killing cancer cells in patients with DLBCL that has relapsed after or is refractory to at least two treatments. When deciding on a course of treatment, it is useful for physicians to know which frequently described clinical characteristics of DLBCL affect the activity and tolerability of selinexor. We found that selinexor showed similar activity and tolerability across most of the frequently described clinical characteristics assessed. Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients < 65 vs. >= 65 years, and for those with lymphocyte counts >= 1000/mu L vs. < 1000/mu L or lactate dehydrogenase <= ULN vs. > ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL.

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study

Cavallo, Federica;
2022

Abstract

Simple Summary Diffuse large B-cell lymphoma (DLBCL) is a complex disease. A combination of immunotherapy and chemotherapy is used to treat DLBCL at initial diagnosis. Additional treatments are available when DLBCL does not respond to initial treatment; however, for many patients, DLBCL will stop responding to treatment (relapse) or may not respond at all (refractory). Selinexor is a novel, oral medication that belongs to a class of drugs called selective inhibitors of nuclear export, and it works by killing cancer cells in patients with DLBCL that has relapsed after or is refractory to at least two treatments. When deciding on a course of treatment, it is useful for physicians to know which frequently described clinical characteristics of DLBCL affect the activity and tolerability of selinexor. We found that selinexor showed similar activity and tolerability across most of the frequently described clinical characteristics assessed. Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients < 65 vs. >= 65 years, and for those with lymphocyte counts >= 1000/mu L vs. < 1000/mu L or lactate dehydrogenase <= ULN vs. > ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL.
14
3
791
805
SADAL study; diffuse large B-cell lymphoma; exportin 1; selinexor
Zijlstra, Josée M; Follows, George; Casasnovas, Rene-Olivier; Vermaat, Joost S P; Kalakonda, Nagesh; Choquet, Sylvain; Hill, Brian; Thieblemont, Catherine; Cavallo, Federica; Cruz, Fatima De la; Kuruvilla, John; Hamad, Nada; Jaeger, Ulrich; Caimi, Paolo; Gurion, Ronit; Warzocha, Krzysztof; Bakhshi, Sameer; Sancho, Juan-Manuel; Schuster, Michael; Egyed, Miklos; Offner, Fritz; Vassilakopoulos, Theodoros P; Samal, Priyanka; Ku, Matthew; Xu, Jenny; Corona, Kelly; Chamoun, Kamal; Shah, Jatin; Canales, Miguel; Maerevoet, Marie
File in questo prodotto:
File Dimensione Formato  
cancers-14-00791-v2.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 1.02 MB
Formato Adobe PDF
1.02 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1874749
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact