First-line ibrutinib plus venetoclax for non-blastoid mantle cell lymphoma in patients ≥65 years or with TP53 mutations
Abstract
The phase 3 SYMPATICO study included an open-label cohort to evaluate the efficacy and safety of first-line ibrutinib plus venetoclax in patients with non-blastoid mantle cell lymphoma (MCL) ≥65 years (n=65), or ≥18 years with a TP53 mutation (TP53m) (n=11). Eligible patients received oral ibrutinib 560 mg once daily and venetoclax (5-week ramp-up to 400 mg once daily) for 2 years, then single-agent ibrutinib 560 mg until disease progression or unacceptable toxicity. In total, 78 patients were enrolled. With median time on study of 40.5 months (range, 0.6+ to 46.9), the complete response (CR) rate was 69% (95% CI, 58-79), and the overall response rate was 95% (95% CI, 87-99). The median duration of response was 37.1 months (95% CI, 30.3-not estimable [NE]). Median progression-free survival (mPFS) was 40.2 months (95% CI, 29.4-NE); median overall survival (OS) was not reached (3-year OS rate, 79% [95% CI, 68-86]). In patients ≥65 years, CR rates were 76% (no TP53m) and 44% (with TP53m), mPFS was 40.2 and 22.0 months, and 3-year OS was 85% and 66%, respectively. In adult patients <65 years (with TP53m), the CR rate was 73%, mPFS was 15.4 months, and 3-year OS was 73%. The most common treatment-emergent adverse events were diarrhea (49%), fatigue (37%), neutropenia (35%), and COVID-19 (32%). First-line ibrutinib plus venetoclax showed promising efficacy, with high CR rates and durable remissions, in patients with previously untreated non-blastoid MCL and may be an option for patients ≥65 years or patients of any age with TP53m. NCT03112174
Article Details
Authors (19)
Michael Wang
Marc S Hoffmann
University of Kansas Medical Center, Westwood, Kansas, United States
Tomasz Wróbel
Marek Trneny
David Belada
4th Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic
Fatih Demirken
Dokuz Eylul University, Division of Hematology, Izmir, Turkey, Izmir, Turkey
Panayiotis Panayiotidis
National and Kapodistrian University of Athens, Athens, Greece
Wojciech Jurczak
Pier Luigi Zinzani
12IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
Mary-Margaret Keating
Dalhousie University, Nova Scotia, Nova Scotia, Canada
Sung-Soo Yoon
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Miklos Egyed
Somogy County Moritz Kaposi General Hospital, Kaposvár, Hungary
Constantine S. Tam
40Department of Haematology, Alfred Hospital and Monash University, Melbourne, VIC, Australia
Nathalie A. Johnson
Jewish General Hospital, Montreal, Canada
Edith Szafer Glusman
AbbVie, South San Francisco, California, United States
Jennifer Lin
AbbVie, North Chicago, Illinois, United States
James P. Dean
AbbVie, North Chicago, Illinois, United States
Jutta K. Neuenburg
AbbVie, North Chicago, Illinois, United States
Gottfried von Keudell
Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States