Editor's Note: From December 7 to 10, 2024, the 66th Annual Meeting of the American Society of Hematology (ASH) was held in San Diego, bringing together global experts in hematology to discuss and exchange insights on the latest advancements in the field. Hematology Frontier invited Dr. Gilles Salles from Memorial Sloan Kettering Cancer Center (MSK) to share key findings in lymphoma research and his thoughts on the conference.1. Could you briefly introduce yourself, your field of expertise, and your research focus?
Dr. Gilles Salles: Hello, everyone. I’m Dr. Gilles Salles from Memorial Sloan Kettering Cancer Center (MSK). My primary focus has always been on lymphoma research, particularly B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and indolent lymphomas like follicular lymphoma.
We are living in a remarkable era of breakthroughs in lymphoma treatment. Reflecting on the past, traditional chemotherapy and high-dose regimens have been progressively replaced by innovative approaches. Twenty-five years ago, rituximab’s introduction marked a turning point, opening the door to new treatment possibilities. Since then, cellular therapies, such as CAR-T cell therapy, have gained significant traction. More recently, bispecific antibodies have emerged as promising tools, pushing lymphoma treatment to new heights. These advancements have delivered tangible improvements in patient outcomes.
At the same time, deeper molecular insights into B-cell lymphomas have enabled us to classify different molecular subtypes more accurately, paving the way for personalized treatment strategies tailored to specific lymphoma subtypes.
My team and I are actively tackling challenges in this space. For example, with bispecific antibodies, we’re exploring ways to optimize their clinical application, especially for patients with follicular lymphoma. To further understand the mechanisms behind these antibodies, we’ve conducted both in vitro and in vivo studies. Additionally, we’re analyzing large-scale molecular datasets to identify the most suitable treatment options for patients.
While we may not yet cure every patient, the progress we’ve made is undeniable. These advances represent the collective effort of colleagues from around the world, including those in the United States, China, and other regions. Together, we are making steady strides toward overcoming lymphoma.
2. Could you introduce the research you presented at this conference?
Dr. Gilles Salles: We presented the results of the five-year follow-up analysis of the POLARIX study (NCT03274492). The initial methodology of this study was published in The New England Journal of Medicine in 2022. In this randomized trial, patients aged 18 to 80 were assigned to either the Pola-R-CHP regimen (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone) or the standard R-CHOP regimen, each for six cycles, followed by two additional cycles of rituximab. The primary endpoint was progression-free survival (PFS).
This extended analysis focused on intermediate- to high-risk DLBCL patients and compared the long-term efficacy and safety of Pola-R-CHP versus R-CHOP. The findings revealed significant and sustained PFS and disease-free survival (DFS) benefits for Pola-R-CHP over R-CHOP.
Key Results:
- Global Intent-to-Treat (ITT) Population: Median follow-up: 60.9 months. Five-year PFS: 64.2% (Pola-R-CHP) vs. 59.1% (R-CHOP), with a hazard ratio (HR) of 0.78 (95% CI: 0.623–0.980). Five-year DFS: 71.3% vs. 65.5% (HR: 0.75; 95% CI: 0.570–0.992). Five-year overall survival (OS): 82.2% vs. 79.6%, with an improved HR of 0.87 compared to the two-year follow-up HR of 0.94.
- Expanded Population: Median follow-up: 60.5 months. Five-year PFS: 63.1% vs. 59.1% (HR: 0.81; 95% CI: 0.652–0.996). Five-year DFS: 69.4% vs. 65.1% (HR: 0.81; 95% CI: 0.625–1.042).
The safety profiles of both regimens were comparable, with no new safety signals observed during long-term follow-up. Notably, patients in the Pola-R-CHP group had fewer lymphoma-related deaths (46 vs. 62) and lower rates of secondary malignancies compared to the R-CHOP group.
These results confirm that Pola-R-CHP is a robust first-line treatment option for intermediate- to high-risk DLBCL, offering sustained clinical benefits and a favorable safety profile.
3. What significant advancements or breakthroughs presented at this conference caught your attention, and how might they influence clinical diagnosis and treatment?
Dr. Gilles Salles: This year’s conference showcased remarkable progress in lymphoma research. For instance, Chinese researchers made groundbreaking discoveries using advanced imaging mass cytometry technology. They conducted detailed analyses of the tumor microenvironment in EBV-positive DLBCL, revealing its immune-suppressive characteristics and identifying the internal regulatory mechanisms responsible for this suppression (Abstract No. 452). They also highlighted the critical role of the tumor immune microenvironment (TIME) in the early progression of follicular lymphoma (Abstract No. 1621).
In the realm of immunotherapy, an exciting study demonstrated that a ketogenic diet can enhance CAR-T cell anti-tumor efficacy through β-hydroxybutyrate (Abstract No. 4). These findings open new doors for optimizing immunotherapy and exploring innovative treatment approaches.
Such advancements are poised to have a profound impact on clinical practice. On the diagnostic front, molecular classification continues to improve, enabling the identification of optimal treatments tailored to individual patient profiles. This enhanced precision not only increases treatment efficacy but also offers greater hope for patients with lymphoma.
4. What insights did you gain from this conference, and how might they influence your clinical practice and research?
Dr. Gilles Salles: The ASH conference provided an invaluable platform for exchanging ideas with global experts and staying updated on the latest advancements. We gained significant insights into CAR-T cell therapies and learned more about translating clinical trial results into real-world applications.
The emergence of new therapies has deepened our understanding of lymphoma and provided direct benefits to patients, while also driving advancements in the broader medical field. These insights will undoubtedly shape my clinical practice and guide future research, enabling us to continue advancing lymphoma treatment and improving patient outcomes.
