Potential Impact of Classification of R/R Diffuse Large B-Cell Lymphoma Microenvironment Archetypes on Patient Treatment and Outcomes
At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, Michael Green, PhD, MD Anderson Cancer Center, Houston, Texas, discusses updates immunomodulatory and cellular therapies and relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) microenvironment archetypes as pertains to patient outcomes.
Transcript:
Hi, I am Michael Green. I'm an associate professor and vice chair for research in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center. I’m here at the Lymphoma Leukemia & Myeloma Winter Symposium in beautiful Miami, Florida.
This morning, I gave a presentation focused on microenvironment archetypes for large B-cell lymphoma. As we know, most of the subtyping strategies for large B-cell lymphoma to date have been tumor-centric. They've been driven by either transcriptional profiles like cell of origin subtype, or dark zone signature, or by tumor genetic profiles like the NCI clusters and the Dana-Farber clusters.
But now we have a range of different immunomodulatory agents and cellular therapies that show a large degree of efficacy for large cell lymphoma. We're very interested in how the microenvironment may change responses or predispose to better or worse outcomes for those patients.
We performed a single-cell study using single-cell profiling of a cohort of 110 relapsed/refractory large B-cell lymphomas, profiling a total of close to a million cells, and used a variety of approaches to identify recurring patterns of cellular cell type associations within the microenvironment. We really distilled it down to 3 major, what we call, lymphoma microenvironment archetype profiles, or LymphoMAPs. One of these is relatively T-cell-depleted, driven by fibroblasts and macrophages. We call that FMAC archetype. Two of them are quite T-cell rich, but one has a healthy T-cell compartment driven by lymph node stromal cells, we call that the lymph node (LN) subtype and 1 has a very exhausted CD8 T-cell compartments, we call it the T-exhausted archetype (TEX).
It would make sense, if driven by T-cell subtypes, these would have associations with outcome and CAR T-cell therapy. We evaluated this within available expression profiling data from the ZUMA-7 randomized phase 3 study of [axicabtagene ciloleucel] (axi-cel) compared to standard of care chemo with autologous stem cell rescue in second-line large B-cell lymphoma. Indeed, we found that patients with a healthy LN-like archetype had a significant benefit from axi-cell over standard of care. Whereas patients with the TEX archetype had no significant benefit over standard of care and it was an intermediate level of benefit within the FMAC archetype that's T-cell depleted.
We're using this information now to move forward and try and define adaptive strategies in future clinical studies at MD Anderson. We'll be interested to see also how they relate to responses with bispecific antibodies and other agents. Thank you.
Source:
Green M. Updates in Basic Science and Diagnostic Classification: Relapsed/Refractory Diffuse Large B-Cell Lymphoma Microenvironment Archetypes (LymphoMAPs). Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, Florida.
