Experts Prepare for Several Key MCL Presentations at ASH 2025

Research breakthroughs in metabolic reprogramming–driven resistance and next-generation targeted inhibition in mantle cell lymphoma (MCL) are poised to take center stage at the 2025 ASH Annual Meeting & Exposition, with new data highlighting both the emergence of pirtobrutinib-tolerant persister cells and the promise of first-in-class BTK-MALT1 fusion inhibitors.

In anticipation of the meeting, OncLive® collected exclusive commentary from:

• Wei Wang, MD, PhD, an assistant professor in the Department of Hematopathology, Division of Pathology/Lab Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas
• Vivian Changying Jiang, PhD, an assistant professor in the Department of Lymphoma/Myeloma - Research, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center
• Preetesh Jain, MBBS, MD, DM, PhD, an assistant professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center

Read on for further insights about the MCL presentations these experts are most excited to see.

330 - The switch of TCA cycle mode determines the fate of pirtobrutinib-tolerant persister cells1

Presentation time: Saturday, December 6, 2025, 5:15 to 5:30 PM EST

Wang: Drug-tolerant persister [DTP] cells are increasingly recognized as a key contributor to therapy resistance in patients with cancer. In MCL, the mechanisms by which DTP cells adapt to treatments and develop stable resistance to systemic therapies remain poorly understood. This work, for the first time, studies the emergence and development of pirtobrutinib (Jaypirca)-tolerant persister cells in MCL, driven by metabolic reprogramming. It may mark the start of a new era in understanding resistance to BTK inhibitors in MCL, moving beyond genetic alterations. Targeting the dedifferentiated state of DTP cells, rather than oncogenic lesions, offers a transformative strategy to overcome therapy resistance in MCL.

390 - First-in-class dual BTK-MALT1 fusion inhibitors for treating resistant Mantle Cell Lymphoma2

Presentation time: Saturday, December 6, 2025, 5:15 to 5:30 PM EST

Jiang: Relapsed/refractory MCL remains a major challenge in B-cell malignancies. This study introduces a first-in-class BTK-MALT1 fusion inhibitor, a single molecule that blocks two critical signaling nodes. These agents demonstrate superior efficacy compared with combining single-target agents and a favorable safety profile in patient-derived models and in vivo, paving the way for a new era in treating [patients with] aggressive lymphomas.

663 - Sonrotoclax (BGB-11417) monotherapy in patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: Early results from A phase 1/2 study3

Presentation time: Sunday, December 7, 5 to 5:15 PM EST

Jain: One [presentation] that is important to look at is the sonrotoclax study, which is an oral abstract. I ran the phase 1 study [of sonrotoclax] at MD Anderson, and then phase 2 was taken over by Michael Wang, MD, [of MD Anderson Cancer Center]. That study is good, and we should look at that BCL-2 antagonist as an alternative agent for patients with MCL.

References

1. Wang W, Cai Q, Liu Y, et al. TCA cycle mode switch determines the fate of pirtobrutinib-tolerant persister cells in mantle cell lymphoma. Blood. 2025;146(suppl 21):2544-2560. doi:10.1182/blood.2024026919
2. Jiang V, Zhou M, Nie L, et al. First-in-class dual BTK-MALT1 fusion inhibitors for treating resistant mantle cell lymphoma. Presented at: 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract 390.
3. Wang M, Song Y , Hermine O, et al. Sonrotoclax (BGB-11417) monotherapy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: Early results from a phase 1/2 study. Presented at: 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract 663.