Page 172 - Haematologica Vol. 109 - July 2024

ARTICLE - Non-Hodgkin Lymphoma
Autologous stem cell transplant in fit patients with refractory or early relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy
Aung M. Tun,1,2* Yucai Wang,1* Seth Maliske,3 Ivana Micallef,1 David J. Inwards,1 Thomas M. Habermann,1 Luis Porrata,1 Jonas Paludo,1 Jose Villasboas Bisneto,1 Allison Rosenthal,4 Mohamed A. Kharfan-Dabaja,5 Stephen M. Ansell,1 Grzegorz S. Nowakowski,1 Umar Farooq3 and Patrick B. Johnston1
1Division of Hematology, Mayo Clinic, Rochester, MN; 2Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas, Kansas City, KS; 3Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA; 4Internal Medicine, Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ and 5Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA
*AMT and YW contributed equally as first authors.
Abstract
Chimeric antigen receptor T-cell therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (e.g., lack of resources for chimeric antigen receptor T-cell therapy, chemosen- sitive relapses). We retrospectively studied 230 patients with refractory or early relapsed DLBCL who underwent ST and ASCT. The median line of ST was one (range, 1-3). Best response before ASCT was complete response in 106 (46%) and partial response in 124 (54%) patients. The median follow-up after ASCT was 89.4 months. The median progression-free (PFS) and overall survival (OS) were 16.1 and 43.3 months, respectively. Patients relapsing between 6 to 12 months after frontline therapy had a numerically better median PFS (29.6 months) and OS (88.5 months). Patients who required one line of ST, compared to those requiring more than one line, had a better median PFS (37.9 vs. 3.9 months; P=0.0005) and OS (68.3 vs. 12.0 months; P=0.0005). Patients who achieved complete response had a better median PFS (71.1 vs. 6.3 months; P<0.0001) and OS (110.3 vs. 18.9 months; P<0.0001) than those in partial response. Patients who achieved complete response after one line of ST had the most favorable median PFS (88.5 months) and OS (117.2 months). Post-ASCT survival outcomes of patients with refractory or early relapsed DLBCL appeared reasonable and were particularly favorable in those who re- quired only one line of ST to achieve complete response before ASCT, highlighting the role of this procedure in select pa- tients with chemosensitive disease.
Correspondence: A.M. Tun atun@kumc.edu
P.B. Johnston
johnston.patrick@mayo.edu
Received: Accepted: Early view:
November 18, 2023. January 11, 2024. January 18, 2024.
https://doi.org/10.3324/haematol.2023.284704
©2024 Ferrata Storti Foundation Published under a CC BY-NC license
Introduction
Diffuse large B-cell lymphoma (DLBCL), the most common type of aggressive non-Hodgkin lymphoma, constitutes ap- proximately 30% of newly diagnosed cases of non-Hodgkin lymphoma each year in the United States.1,2 Approximately 30-40% of patients encounter relapsed or refractory dis- ease after frontline immunochemotherapy, and their survival outcomes are generally unfavorable – particularly in those with refractory disease or an early relapse occurring within 12 months of initial diagnosis (or frontline treatment), as reported by multiple studies including those by the Center for International Blood and Marrow Transplant Research
(CIBMTR), the Molecular Epidemiology Resource of the Uni- versity of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence, as well as the CORAL study.3-14 To improve outcomes of such patients, three phase III ran- domized clinical trials were conducted in patients with refractory disease or an early relapse within 12 months of treatment completion, comparing chimeric antigen receptor T-cell (CAR-T) products (axicabtagene ciloleucel in ZUMA-7, tisagenlecleucel in BELINDA, lisocabtagene maraleucel in TRANSFORM) to the then standard-of-care salvage chemo- therapy (ST) followed by high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT), which established axicabtagene ciloleucel and lisocabtagene maraleucel as the
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