Journal article
Multi-Institutional Study of ALK-Positive Large B-Cell Lymphoma: Outcomes in the Era of ALK Inhibitors and Biologically Informed Therapies
American journal of hematology, Vol.10(12), pp.2185-2194
12/2025
DOI: 10.1002/ajh.70058
PMID: 40899786
Abstract
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma with poor outcomes using standard chemotherapy. In this multi-institutional retrospective study, we analyzed 39 cases of ALK+ LBCL identified at six US academic centers from 2002 to 2024, with treatment including conventional cytotoxic regimens in frontline and biologically informed and nonchemotherapy-based strategies in the relapsed setting. Ninety-two percent of patients received frontline anthracycline-based chemotherapy; 43% received intensified regimens, and 15% underwent upfront autologous stem cell transplantation (ASCT). Despite these approaches, outcomes remained poor. At a median follow-up of 5.4 years, median event-free survival (EFS) was 0.6 years (95% CI, 0.4-0.9), and median overall survival (OS) was 1.5 years (95% CI, 1.3-NR). One- and five-year EFS rates were 28% and 17%, while corresponding OS rates were 72% and 42%, respectively. Advanced stage and high IPI scores were associated with inferior outcomes. Twelve patients received ALK inhibitors, with alectinib showing more durable responses than crizotinib. Lenalidomide and immune checkpoint inhibitors also demonstrated activity, including durable complete responses. Five patients underwent allogeneic stem cell transplantation, with three achieving sustained remission. In conclusion, our findings highlight the limited benefit of chemotherapy, even when intensified or followed by ASCT, and support the integration of biologically targeted therapies, which may have contributed to improved OS in our cohort compared to historical outcomes. Prospective, collaborative studies are needed to better understand disease biology and define optimal use of modern therapies in this rare lymphoma.
Details
- Title: Subtitle
- Multi-Institutional Study of ALK-Positive Large B-Cell Lymphoma: Outcomes in the Era of ALK Inhibitors and Biologically Informed Therapies
- Creators
- Suheil Albert Atallah-Yunes - Mayo ClinicChijioke C Nze - The University of Texas MD Anderson Cancer CenterRebecca L King - Mayo ClinicMatthew J Rees - Mayo ClinicJuan Pablo Alderuccio - University of MiamiMarcus Watkins - Washington University in St. LouisBrad S Kahl - Washington University in St. LouisNeela Easwar - Weill Cornell MedicineSamuel Yamshon - Weill Cornell MedicineAditya Ravindra - University of IowaUmar Farooq - University of IowaAllison C Rosenthal - Mayo Clinic in FloridaJavier L Munoz - Mayo Clinic in FloridaEstela M Rojas-Neira - The University of Texas MD Anderson Cancer CenterAmy A Ayers - The University of Texas MD Anderson Cancer CenterMuhamad Alhaj Moustafa - Mayo Clinic in FloridaThomas M Habermann - Mayo ClinicThomas E Witzig - Mayo ClinicStephen M Ansell - Mayo ClinicGrzegorz S Nowakowski - Mayo ClinicJean L Koff - Emory UniversityChristopher R Flowers - The University of Texas MD Anderson Cancer CenterYucai Wang - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- American journal of hematology, Vol.10(12), pp.2185-2194
- DOI
- 10.1002/ajh.70058
- PMID
- 40899786
- NLM abbreviation
- Am J Hematol
- ISSN
- 1096-8652
- eISSN
- 1096-8652
- Publisher
- WILEY
- Language
- English
- Electronic publication date
- 09/03/2025
- Date published
- 12/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984958611202771
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