CAR T-Cell therapy: Understanding Progression in Mantle Cell Lymphoma Amidst Promising Results
August 16, 2025
A significant new study focusing on CAR T-cell therapy for relapsed or refractory Mantle Cell Lymphoma (MCL) indicates that while the treatment shows considerable promise, disease progression remains a challenge for a notable portion of patients. The findings, published on August 5th, stem from an extensive analysis of 384 individuals across 15 global cancer centers.
This research, appearing in the journal *Blood Advances*, delves into the characteristics of the 135 patients who experienced disease progression following CAR T-cell treatment. the median timeframe from treatment initiation to progression was identified as six months, a crucial statistic for understanding treatment durability.
key Findings on disease Progression
The study highlighted several factors associated with progression.The patient cohort experiencing advancement in their MCL typically comprised 74% males, with a median age of 67. notably, a vast majority, 98%, had previously received treatment with a Bruton tyrosine kinase (BTK) inhibitor before undergoing CAR T-cell therapy, with 63% showing a response to that prior treatment.
The median number of prior therapies before CAR T-cell infusion was three, with a range of one to nine. High-risk features were frequently observed, including a *TP53* mutation in 68% of patients, Ki67 levels of at least 50% in 69%, central nervous system (CNS) involvement in 16%, and blastoid or pleomorphic MCL in 25% of cases.
Bridging therapy-treatment given while waiting for CAR T-cell manufacturing-was utilized by most patients (73%), with 60% of those whose responses were assessed showing resistance to this bridging treatment.
Treatment Landscape and Outcomes
Two CAR T-cell therapies are currently approved by the FDA for MCL: brexucabtagene autoleucel (brexu-cel, Tecartus), available as 2020 after at least one prior therapy, and lisocabtagene maraleucel (liso-cel, Breyanzi), approved in 2024 for use after at least two prior lines, including BTK inhibitor therapy. Manufacturers report notable initial response rates, with brexu-cel showing a 91% overall response rate and a median progression-free survival (PFS) of 25.8 months, while liso-cel has an 83% ORR and a median PFS of 15.3 months. Though, neither therapy is currently considered curative.
Among the patients who progressed post-CAR T-cell therapy, initial complete responses were achieved by 64%, with partial responses in 27% and stable disease in 16%. Within this group that ultimately progressed, high-risk features were also evident at the time of progression: 37% had blastoid/pleomorphic morphology, 77% had Ki67 ≥ 50%, and 51% had a *TP53* mutation. Furthermore, 11 out of 22 patients with prior CNS disease also showed CNS involvement at the time of progression. A small percentage, 10% of those tested, exhibited CD19-negative disease following progression.
Subsequent Treatment Options and Survival
For patients experiencing disease progression,treatment strategies varied. Seventeen patients received no further therapy, 13 underwent local treatment, and 105 received systemic therapy. among the subsequent systemic treatments, chemoimmunotherapy yielded an ORR of 40% in 22 patients, pirtobrutinib had a 36% ORR in 17 patients, and bispecific antibodies demonstrated a 67% ORR in 13 patients.
The prognosis for patients with disease progression after CAR T-cell therapy was challenging, with a median PFS of 2.5 months and a median overall survival (OS) of 5.4 months. Factors associated with poorer outcomes included a lack of initial response to CAR T-cell therapy and a shorter time to progression (less then three months) after infusion.
The study authors concluded by emphasizing the ongoing challenge presented by disease progression in R/R MCL patients treated with CAR T-cell therapy, establishing this research as a critical benchmark for future advancements.
| Factor | Prevalence in Progressing Patients |
|---|---|
| Male Gender | 74% |
| Prior BTK Inhibitor Treatment | 98% |
| Median Prior Therapies | 3 (1-9) |
| TP53 Mutation | 68% |
| Ki67 ≥ 50% | 69% |
| CNS Involvement (prior) | 16% |
The advancement of resistance or progression after CAR T-cell therapy is a critical area of research in oncology. Understanding the patient profiles and disease characteristics that predict these outcomes is vital for optimizing treatment strategies.
Did You Know? The median survival for Mantle Cell Lymphoma patients experiencing disease progression after CAR T-cell therapy was reported as just over five months in this extensive international study.
As research advances,identifying patients most likely to benefit from CAR T-cell therapy and developing effective second-line treatments remain paramount goals in improving outcomes for individuals with Mantle Cell Lymphoma.
What are your thoughts on the current landscape of CAR T-cell therapy for challenging blood cancers like MCL?
How can we better stratify patients to predict response and minimize progression?
Evergreen Insights: Navigating CAR T-Cell Therapy for MCL
CAR T-cell therapy represents a significant leap in treating hematologic malignancies, including Mantle Cell lymphoma (MCL). This personalized immunotherapy involves re-engineering a patient’s own T-cells to target and destroy cancer cells expressing a specific antigen, such as CD19. While groundbreaking, its request in relapsed or refractory (R/R) settings, where the cancer has returned or resisted previous treatments, presents unique challenges.
Understanding the Disease and Treatment Landscape
Mantle Cell Lymphoma is an aggressive B-cell non-Hodgkin lymphoma characterized by the presence of cyclin D1 or its regulatory-associated protein D1.its refractory nature frequently enough necessitates advanced treatment modalities. FDA-approved CAR T-cell therapies like brexu-cel and liso-cel offer new hope, but the biological complexity of MCL, including genetic mutations like *TP53* and high proliferation rates (indicated by Ki67), can influence treatment efficacy.
Factors Influencing CAR T-Cell Therapy Success
- Disease Burden and Prior Treatments: The number of prior therapies and the patient’s overall health status significantly impact outcomes. A history of BTK inhibitor treatment, commonly used in MCL, is a key factor to consider.
- High-Risk Features: The presence of specific genetic mutations (e.g., *TP53*) and aggressive disease characteristics (e.g.,blastoid morphology,high Ki67) are associated with a higher likelihood of treatment failure or progression.
- Tumor Microenvironment: The immune microenvironment surrounding the lymphoma cells can affect T-cell function and persistence, perhaps leading to resistance.
- Antigen loss: In certain specific cases, cancer cells may stop expressing the target antigen (like CD19), rendering the CAR T-cells ineffective.
Navigating Progression and Future Directions
The documented progression rates highlight the need for ongoing research into optimizing CAR T-cell therapy, including exploring novel targets, combination strategies, and improved methods for overcoming resistance mechanisms. For patients experiencing progression, a multidisciplinary approach to select subsequent therapies, potentially including newer agents like bispecific antibodies or novel small molecules, is crucial.
Continuous monitoring and early intervention are key to managing the complexities of CAR T-cell therapy in R/R MCL. Patients considering or undergoing this treatment should engage in open discussions with their healthcare team about potential risks, benefits, and the importance of post-treatment surveillance.
Pro Tip: Always consult with your oncologist to understand how personalized treatment plans, including CAR T-cell therapy, align with your specific diagnosis and medical history.
For more facts on Mantle Cell Lymphoma treatments and research, visit reputable sources like the National Cancer Institute and the Lymphoma Research Foundation.
Frequently Asked Questions about CAR T-Cell Therapy and MCL progression
What is CAR T-cell therapy for Mantle Cell Lymphoma (MCL)?
CAR T-cell therapy is an advanced immunotherapy that involves genetically modifying a patient’s T-cells to better recognize and attack cancer cells, specifically targeting CD19 in Mantle Cell Lymphoma.
What percentage of MCL patients experience disease progression after CAR T-cell therapy?
According to a recent study, approximately one-third of patients with relapsed or refractory Mantle Cell Lymphoma experience disease progression following CAR T-cell therapy.
What are the median time to progression for MCL patients on CAR T-cell therapy?
The median time from CAR T-cell infusion to disease progression in Mantle Cell lymphoma patients was reported as six months in a recent international study.
Which high-risk features are associated with CAR T-cell therapy progression in MCL?
High-risk features linked to CAR T-cell therapy progression in Mantle Cell lymphoma include TP53 mutations, high Ki67 levels (≥50%), and central nervous system (CNS) involvement.
What is the prognosis for MCL patients who experience disease progression after CAR T-cell therapy?
The prognosis for patients with Mantle Cell Lymphoma experiencing disease progression after CAR T-cell therapy is challenging, with median progression-free survival of 2.5 months and median overall survival of 5.4 months reported.
What treatments follow CAR T-cell therapy for progressing MCL?
Following disease progression, patients with Mantle Cell Lymphoma may receive subsequent therapies such as chemoimmunotherapy, pirtobrutinib, or bispecific antibodies, with varying response rates.
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