Increase Testing Rates and Tailored First-Line Treatments Represent Unmet Needs in High-Risk MCL

Chemoimmunotherapy was the most common first-line treatment given to patients with high-risk mantle cell lymphoma (MCL), according to findings from a real-world retrospective study. High-risk MCL being associated with a poor prognosis, those in the high-risk cohort has similar MCL international Prognostic Index (MIPI) scores and first-line treatment patterns compared with patients with MCL who are not high-risk, according to Preteesh Jain, MD, MBBS, DM, PhD.

In addition to the widespread use of chemoimmunotherapy in high-risk patients, testing rates for TP53 mutations and Ki67 proliferation were low in the overall MCL cohort, underscoring the need for increased education about the importance of evaluating these factors in patients with MCL, Jain added.

In the real-world retrospective cohort study of the Flatiron Health Research Database, which was presented at the 2025 ASH Annual Meeting and Exposition, investigators evaluated the first-line treatment patterns of all patients with MCL (n = 1657) compared with a high-risk subset of patients with MCL (n = 465).¹ Chemoimmunotherapy (bendamustine plus rituximab [Rituxan]) was the most common in all patients with MCL and the high-risk subset, at rates of 53.5% and 47.7%, respectively. BTK inhibitor monotherapy or combinations were given to 4.8% of all patients with MCL and 7.1% of patients with high-risk MCL. The median real-world time to next treatment or death for all patients with MCL was 23.0 months (95% CI, 19.8-27.1) vs 12.1 months (95% CI, 10.3-15.9) in the high-risk cohort.

“These practice patterns are important to note and might spark increased interest in using up-front [BTK] combination triplets in the [high-risk MCL population] in community [practice],” Jain, an assistant professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with OncLive®.

In the interview, Jain explored results from the real-world analysis, noting the insufficiencies within the MCL community that they expose and how the community can move forward. In a previous article, Jain broke down data from phase 1 Window-3 trial (NCT05495464), which evaluated acalabrutinib (Calquence) plus rituximab followed by brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with previously untreated, high-risk MCL.²

Onclive: What are the limitations of the MIPI score for MCL prognosis?

Jain: [For this analysis,] we looked at a real-world cohort from the Flatiron Health Research Database, where patients have been treated on standard-of-care treatments. Then we looked at a subset of high-risk patients who were traditionally defined by the MIPI score, Ki67 [proliferation], and blastoid and pleomorphic features.¹

The MIPI score, in my opinion, does have limitations. With the new understanding of MCL, we are looking at patients who might be qualified as high-risk per MIPI but have indolent disease, and vice versa. Incorporation of TP53 mutation and other biologic parameters in a uniform manner in first-line diagnosis for patients with MCL is important to develop and evaluate.

One of the important limitations [with disease characterization for patients with MCL] is the assessment of TP53 mutations. [Conducting next-generation sequencing], along with TP53 fluorescence in situ hybridization. These 2 are key [tests], in addition to other types of tests like genomic assessments, which are also important to note.

How was the study designed?

[This study sought to] evaluate high-risk patients with MCL primarily because it is a rare cohort and a less-understood type of MCL. We wanted to evaluate real-world practice patterns within this [less common subgroup of patients]. [We sought to evaluate treatment patterns like] whether chemoimmunotherapy or BTK inhibitor–based therapy was received and in which settings. Based on [these patterns], the study was able to identify that the majority of patients did receive chemoimmunotherapy, rather than BTK inhibitor-based therapy.

What were the key findings of the real-world analysis?

The most important features of the analysis to notice are that chemoimmunotherapy does not provide durable remission rates in high-risk MCL. There are patients [receiving first-line chemoimmunotherapy] who frequently relapse and then receive a second-line BTK inhibitor. If patients have progression in the first 6 to 24 months after induction, they do not respond well. This interaction has been reported in the past, but in a high-risk MCL cohort of patients, [early progression] is more noticeable compared with other MCL cohorts with different levels of risk. Subsequently, as the number of lines of therapy increases and remission duration decreases.

What are the clinical implications and next steps for this analysis?

There are so many missing points since many of [the TP53 mutation and Ki67 proliferation tests for patients included in this analysis] were not done in the first-line setting. Those things were missed. There is a need for more education in the community with respect to MCL. It is a rare disease, but there are [genomic] tests available all over the world. Utilization of the currently available parameters will help us refine the risk of these patients with MCL.

The next step is to evaluate a larger cohort of patients and gather more information from BTK inhibitor–treated, high-risk cohorts of patients and look at their outcomes.

References

1. Jain P, Teschemaker A, Ibrahim E, et al. Real-world treatment patterns and clinical outcomes in high-risk mantle cell lymphoma: a retrospective analysis. Blood. 2025;146(suppl 1):4482. doi:10.1182/blood-2025-4482
2. Kandel R. Frontline acalabrutinib/rituximab followed by brexu-cel shows synergy and safety in high-risk MCL. OncLive. January 7, 2026. Accessed January 7, 2026. https://www.onclive.com/view/frontline-acalabrutinib-rituximab-followed-by-brexu-cel-shows-synergy-and-safety-in-high-risk-mcl