Treatment-related outcomes and patterns of relapse in secondary CNS involvement by large B-cell lymphoma
Abstract
Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.
Article Details
Authors (61)
Juan Pablo Alderuccio
20Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
Diva Baggio
2Department of Haematology, University College London Hospital, London, United Kingdom
Sunwoo Han
Paola Ghione
4Memorial Sloan Kettering Cancer Center, New York, NY
Imran Nizamuddin
5Division of Oncology, Washington University, St. Louis, MO
Jahanzaib Khwaja
2Department of Haematology, University College London Hospital, London, United Kingdom
Aditi Saha
6Moffitt Cancer Center, Tampa, FL
Ning Dong
Yucai Wang
State Key Laboratory of Immune Response and Immunotherapy, Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine
Hua-Jay J. Cherng
8Columbia University Irving Medical Center, New York, NY
Seda Tolu
8Columbia University Irving Medical Center, New York, NY
Nina Wagner-Johnston
9The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
Thomas A. Ollila
6Division of Hematology and Oncology, Department of Medicine, Brown University, Providence, RI
Natalie Grover
11Division of Hematology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
Jean L. Koff
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
Amrita Desai
13Division of Hematology/Medical Oncology, Oregon University, Portland, OR
Praveen Ramakrishnan Geethakumari
14Division of Hematology and Oncology, UT Southwestern, Dallas, TX
Tamara K. Moyo
15Levine Cancer Institute, Atrium Health, Charlotte, NC
Jose Sandoval-Sus
16Moffitt Malignant Hematology at Memorial Healthcare System, Pembroke Pines, FL
Narendranath Epperla
University of Utah, Salt Lake City, Utah, United States
Danielle S. Wallace
18Division of Hematology/Oncology, Wilmot Cancer Institute University of Rochester Medical Center, Rochester, NY
Manali Kamdar
Rita Tavarozzi
4Memorial Sloan Kettering Cancer Center, New York, NY
Alexey Danilov
20City of Hope, Duarte, CA
Han Tun
21Mayo Clinic Florida, Jacksonville, FL
Javier Muñoz
Mayur Narkhede
23University of Alabama, Birmingham, AL
Joanna M. Rhodes
24Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
Anca Prica
Princess Margaret Cancer Centre, Toronto
Andrea Kuhnl
26King's College Hospital London, London, United Kingdom
Adrian Maraj
27St James Hospital, Dublin, Ireland
Jessica Okosun
28Department of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
Jeffery Smith
29Clatterbridge Cancer Center, Liverpool, United Kingdom
Wendy Osborne
30Department of Haematology, Freeman Hospital, Newcastle University, Newcastle, United Kingdom
Victoria Calvert
30Department of Haematology, Freeman Hospital, Newcastle University, Newcastle, United Kingdom
Dima El-Sharkawi
14Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
Ammar Hilali
31Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
Graham P. Collins
32Department of Clinical Haematology, Oxford University Hospital, Oxford, United Kingdom
Kim Linton
33Manchester Cancer Research Center, Manchester, United Kingdom
Nagah Elmusharaf
34Department of Haematology, University Hospital of Wales, Cardiff, United Kingdom
Anna Santarsieri
35Department of Haematology, Cambridge University Hospitals, Cambridge, United Kingdom
Farheen Karim
36The Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
Firas Baidoun
21Mayo Clinic Florida, Jacksonville, FL
Sarah E. Monick
22Mayo Clinic Arizona, Phoenix, FL
Iris Margalit Trutzer
9The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
Jones Can
16Moffitt Malignant Hematology at Memorial Healthcare System, Pembroke Pines, FL
Amy Ayers
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
Jacopo Calabrese De Feo
4Memorial Sloan Kettering Cancer Center, New York, NY
John Sharp
17Division of Hematology, Ohio State University, Columbus, OH
Nilanjan Ghosh
5Levine Cancer Institute/Advocate Health, Wake Forest University School of Medicine, Charlotte, NC
Rachel Treitman
19Division of Hematology, University of Colorado, Aurora, CO
Avyakta Kallam
10Duarte Cancer Center, City of Hope Medical Center, Duarte, CA
Izel Okcu
7Mayo Clinic Rochester, Rochester, MN
Chathuri Abeyakoon
25Princess Margaret Cancer Center, Toronto, Canada
William Hann
28Department of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
Aisling Barrett
32Department of Clinical Haematology, Oxford University Hospital, Oxford, United Kingdom
Vismay Deshani
37Christie NHS Foundation Trust, Manchester, United Kingdom
Brad S. Kahl
30Division of Oncology, Washington University School of Medicine, St. Louis, MO
Julio C. Chavez
4Moffitt Cancer Center, Tampa, FL
Adam J. Olszewski
10Department of Medicine, Brown University, Providence, RI
Kate Cwynarski
15Department of Haematology, University College London, London, United Kingdom