Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes.
Por:
Casasnovas RO, Follows G, Zijlstra JM, Vermaat JSP, Kalakonda N, Choquet S, Neste EVD, Hill B, Thieblemont C, Cavallo F, la Cruz F, Kuruvilla J, Hamad N, Jaeger U, Caimi PF, Gurion R, Warzocha K, Bakhshi S, Sancho JM, Schuster M, Egyed M, Offner F, Vassilakopoulos TP, Samal P, Ku M, Ma X, Chamoun K, Shah J, Canales M, Maerevoet M, Shacham S, Kauffman MG and Goy A
Publicada:
1 ene 2022
Ahead of Print:
22 jul 2021
Resumen:
BACKGROUND: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. PATIENTS AND METHODS: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. RESULTS: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels = 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. CONCLUSIONS: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.
Filiaciones:
Casasnovas RO:
Hématologie Clinique and INSERM 1231, CHU Dijon Bourgogne, Dijon, France
Follows G:
Addenbrooke's Hospital, Cambridge, United Kingdom
Zijlstra JM:
Amsterdam University Medical Center, Vrije Universiteit, Cancer Center, Amsterdam, The Netherlands
Vermaat JSP:
Leiden University Medical Center, Leiden, The Netherlands
Kalakonda N:
University of Liverpool, Liverpool, United Kingdom
Choquet S:
Hôpital Pitié Salpêtrière, Paris, France
Neste EVD:
Cliniques Universitaires Saint-Luc, Brussels, Belgium
Hill B:
Cleveland Clinic, Cleveland, OH
Thieblemont C:
AP-HP, Hopital Saint-Louis, Hémato-oncology, DMU DHI, Paris, France
Université de Paris, Paris, France
Cavallo F:
Department of Molecular Biotechnologies and Health Sciences, Division of Hematology, University of Turin, Turin, Italy
la Cruz F:
Hospital Universitario Virgen del Rocio, Sevilla, Spain
Kuruvilla J:
Princess Margaret Cancer Center, Toronto, Canada
Hamad N:
St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia
Jaeger U:
Medical University of Vienna, Vienna, Austria
Caimi PF:
UH Seidman Cancer Center, Cleveland, OH
Gurion R:
Institute of Hematology, Rabin Medical Center, Petah Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Warzocha K:
Instytut Hematologii i Transfuzjologii, Warsaw, Poland
Bakhshi S:
Dr. B. R. A. Institute Rotary Cancer Hospital, New Delhi, India
:
Hospital Universitari Germans Trias i Pujol, Barcelona, Spain
Schuster M:
Stony Brook University Hospital Cancer Center, New York, NY
Egyed M:
Teaching Hospital Kaposi Mór, Kaposvár, Hungary
Offner F:
Ghent University Hospital, Ghent, Belgium
Vassilakopoulos TP:
Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
Samal P:
Institute of Medical Sciences & SUM Hospital, Odisha, India
Ku M:
St.Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
Ma X:
Karyopharm Therapeutics, Newton, MA
Chamoun K:
Karyopharm Therapeutics, Newton, MA
Shah J:
Karyopharm Therapeutics, Newton, MA
Canales M:
Hospital Universitario La Paz, Madrid, Spain
Maerevoet M:
Institute Jules Bordet, Brussels, Belgium
Shacham S:
Karyopharm Therapeutics, Newton, MA
Kauffman MG:
Karyopharm Therapeutics, Newton, MA
Goy A:
Hackensack University Medical Center, Hackensack, NJ
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