Mantle Cell Lymphoma: Progression Risks After CAR T-Cell Therapy Highlighted in New Study
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A recent, extensive analysis of 384 patients with relapsed or refractory mantle cell lymphoma (MCL) indicates that approximately one-third experience disease progression following treatment with chimeric antigen receptor (CAR) T-cell therapy. The findings, published August 5 in Blood Advances, underscore the complexities of managing this aggressive blood cancer even with cutting-edge immunotherapies.
Understanding mantle Cell Lymphoma and CAR T-Cell therapy
Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma. CAR T-cell therapy represents a significant advancement in cancer treatment, genetically modifying a patient’s own T cells to recognize and destroy cancer cells.The Food and Drug Management has approved two CAR T-cell therapies for MCL: brexucabtagene autoleucel (brexu-cel, Tecartus) in 2020, and lisocabtagene maraleucel (liso-cel, Breyanzi) in 2024.
Brexu-cel is indicated for patients after at least one prior line of therapy, while liso-cel can be used after at least two prior lines, including a Bruton tyrosine kinase (BTK) inhibitor.Despite the promise of these therapies, the new study reveals a significant risk of disease progression, prompting researchers to investigate contributing factors.
key Findings from the Multicenter Analysis
Researchers from leading cancer centers, including Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, and Mayo Clinic, collaborated on the study. Their analysis focused on the 135 patients who experienced disease progression after CAR T-cell therapy, with a median time to progression of six months.
The patient cohort experiencing progression was predominantly male, with a median age of 67 years. Notably, 98% of these patients had previously received a BTK inhibitor, with 63% demonstrating a response. The median number of prior therapies was three.
Did You know?
Mantle cell lymphoma accounts for approximately 6% of all non-Hodgkin lymphomas in the United States, affecting more men than women.
Patient Characteristics Associated with Progression
Several high-risk features were common among patients who progressed after CAR T-cell therapy. These included a TP53 mutation in 68% of cases,a Ki67 proliferation index of at least 50% in 69%,central nervous system (CNS) involvement in 16%,and blastoid/pleomorphic MCL in 25%. Most patients (73%) received bridging therapy, but 60% of those assessed were refractory to it.
The majority of patients received brexu-cel (87%) or liso-cel (13%), with most undergoing lymphodepletion with fludarabine and cyclophosphamide (87%). Following treatment, 64% achieved a complete response, 27% a partial response, and 16% stable disease.
| Characteristic | Percentage/Median |
|---|---|
| Male Patients | 74% |
| Median Age (Years) | 67 |
| Prior BTK Inhibitor Use | 98% |
| TP53 Mutation | 68% |
| Ki67 ≥ 50% | 69% |
Outcomes Following disease Progression
The median time from CAR T-cell infusion to disease progression was six months, with only 30 patients experiencing progression after more than 12 months. At the time of progression,high-risk features persisted in many patients,including blastoid/pleomorphic morphology (37%),a Ki67 of at least 50% (77%),and a TP53 mutation (51%). CNS involvement was present in 51% of patients with prior CNS disease.
Analysis of CD19 status following progression revealed that 10% of patients had become CD19-negative, possibly contributing to treatment resistance. Following disease progression, 17 patients received no further treatment, 13 received local therapy, and 105 received systemic therapy.
Pro Tip:
Understanding the specific genetic mutations and characteristics of a patient’s MCL is crucial for tailoring treatment strategies and predicting response to therapies.
Response rates to subsequent therapies were as follows: chemoimmunotherapy (40%), pirtobrutinib (36%), and bispecific antibodies (67%). The median progression-free survival (PFS) and overall survival (OS) for patients experiencing progression were 2.5 months and 5.4 months, respectively. A lack of initial response to CAR T-cell therapy and rapid progression (less than three months) were associated with inferior OS.
Future Directions and Clinical Implications
“We confirm the challenging prognosis for patients experiencing [disease progression] following CD19 CAR-T for R/R MCL and establish a benchmark for future,” the authors concluded. These findings highlight the need for improved strategies to address disease progression after CAR T-cell therapy, including novel therapeutic approaches and more refined patient selection criteria. What additional therapies might improve outcomes for patients who relapse after CAR T-cell treatment? How can we better identify patients who are most likely to benefit from this therapy in the first place?
References
- Epstein-Peterson ZD, Lionel AC, Joseph A, et al. Treatment and outcomes of progression of disease post-CAR T-cell therapy in mantle cell lymphoma: a multicenter analysis. Blood Advances. Published August 5, 2025. doi.org/10.1182/bloodadvances.2025016315
- Stallard J. FDA approves CAR T cell treatment for resistant mantle cell lymphoma. Memorial Sloan Kettering Cancer Center. July 31, 2024.Accessed August 15, 2025. https://www.mskcc.org/news/fda-approves-car-t-cell-treatment-for-resistant-mantle-cell-lymphoma
Mantle cell lymphoma research is rapidly evolving, with ongoing clinical trials exploring novel combinations of therapies and strategies to overcome treatment resistance. The development of bispecific antibodies and improved CAR T-cell designs represent promising avenues for enhancing outcomes in this challenging disease. Long-term follow-up of patients receiving CAR T-cell therapy is crucial to fully understand the durability of responses and identify factors associated with late relapses.
Frequently Asked Questions About Mantle Cell Lymphoma and CAR T-Cell Therapy
- What is mantle cell lymphoma? Mantle cell lymphoma is an aggressive type of non-Hodgkin lymphoma that develops in the mantle zone of lymph nodes.
- What is CAR T-cell therapy? CAR T-cell therapy is a personalized cancer treatment that uses a patient’s own immune cells to fight cancer.
- What are the common side effects of CAR T-cell therapy? Common side effects include cytokine release syndrome and neurotoxicity.
- What is the prognosis for patients with relapsed or refractory mantle cell lymphoma? The prognosis varies depending on individual factors,but it is generally considered poor.
- What are the current treatment options for mantle cell lymphoma? Treatment options include chemotherapy, radiation therapy, stem cell transplant, and CAR T-cell therapy.
Disclaimer: This article provides general information and should not be considered medical advice. Please consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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