TP53 ‐Altered Aggressive Large B‐Cell Lymphoma ( LBCL ) Outcomes by Treatment Modality: A Multicenter Cohort From 14 US Centers
Advances in the treatment of large B-cell lymphoma (LBCL) have expanded therapeutic options beyond conventional chemoimmunotherapy to include cellular and targeted therapies. There is growing interest in identifying subsets of LBCL that may benefit from these novel approaches based on histopathologic and molecular features. Molecular subclassification has identified an LBCL A53 phenotype characterized by TP53 alterations, a subgroup historically associated with poor outcomes following standard therapy. To better define progression-free and overall survival outcomes in TP53-altered LBCL in the contemporary treatment era, we conducted a multicenter cohort study evaluating responses to first-, second-, and third-line therapies. Our findings demonstrate that TP53-altered LBCL can be cured with first-line curative intent chemoimmunotherapy. In the second and third-line setting, outcomes did not significantly differ between different treatment approaches, though improved PFS was seen with CAR-T in the second line for double hit patients. This study represents the largest reported cohort of patients with TP53-altered LBCL and provides important insights into treatment outcomes across lines of therapy in the era of novel agents.
Authors
- Reem Karmali (ORCID: https://orcid.org/0000-0003-0984-4376)
- Neil A. Bailey (ORCID: https://orcid.org/0000-0002-3809-3236)
- Bradley M. Haverkos (ORCID: https://orcid.org/0000-0002-3872-0615)
- Hua‐Jay J. Cherng (ORCID: https://orcid.org/0000-0002-8266-8447)
- Brian T. Hill (ORCID: https://orcid.org/0000-0001-8781-3327)
- Nancy Musoke (ORCID: https://orcid.org/0000-0003-4690-7516)
- Alec Hansen (ORCID: https://orcid.org/0009-0008-0272-3428)
- Andrew Ip (ORCID: https://orcid.org/0000-0003-0456-5618)
- Grace Bosma (ORCID: https://orcid.org/0000-0002-2397-2772)
- Steven M. Bair (ORCID: https://orcid.org/0000-0002-0094-0014)
- Brian Hess (ORCID: https://orcid.org/0000-0003-0176-2050)
- Forat Lutfi (ORCID: https://orcid.org/0000-0002-9699-3080)
- Allison M. Bock (ORCID: https://orcid.org/0000-0002-3174-8877)
- Maciej Kabat (ORCID: https://orcid.org/0000-0002-0895-1869)
- Alexander Gorzewski (ORCID: https://orcid.org/0000-0002-0657-1328)
- Joanna Rhodes (ORCID: https://orcid.org/0000-0002-5068-9040)
- Gaston Jean-Louis (ORCID: https://orcid.org/0000-0001-6483-6542)
- Jonathan H. Schatz (ORCID: https://orcid.org/0000-0003-1842-228X)
- Asaad Trabolsi (ORCID: https://orcid.org/0000-0002-2479-1797)
- Mengyang Di (ORCID: https://orcid.org/0000-0001-6165-2617)
- Ajay Major (ORCID: https://orcid.org/0000-0001-7261-1335)
- Tharakeswari Selvakumar (ORCID: https://orcid.org/0000-0002-0827-0887)
- P. Connor Johnson (ORCID: https://orcid.org/0000-0002-3943-6608)
- Cassandra Duarte (ORCID: https://orcid.org/0000-0001-6108-3768)
- Nausheen Ahmed (ORCID: https://orcid.org/0000-0003-4336-4982)
- Ellen K. Kendall (ORCID: https://orcid.org/0000-0001-9533-0974)
- Zachary AK Frosch (ORCID: https://orcid.org/0000-0002-4599-0533)
- M Greenberg
- Diana Abbott
- Daniel Stapor (ORCID: https://orcid.org/0009-0006-5309-8226)
- Manali Kamdar
- Jagar Jasem
- Krish Patel
- Mazyar Shadman
Institutions
- Rutgers, The State University of New Jersey (US)
- Northwestern University (US)
- Fox Chase Cancer Center (US)
- Cleveland Clinic (US)
- Hackensack University Medical Center (US)
- University of Miami (US)
- Colorado School of Public Health (US)
- Medical University of South Carolina (US)
- University of Utah (US)
- Columbia University Irving Medical Center (US)
- Huntsman Cancer Institute (US)
- Massachusetts General Hospital (US)
- Fred Hutch Cancer Center (US)
- Swedish Medical Center (US)
- The University of Kansas Cancer Center (US)
- Sarah Cannon (US)
- Rutgers Cancer Institute (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- European Journal Of Haematology
- Published
- 2026-09-18
- DOI
- https://doi.org/10.1111/ejh.70330
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00