The 18th International Conference on Malignant Lymphoma (ICML), organized by the Institute of Oncology Research (IOR), took place from June 17 to 21, 2025, in Lugano, Switzerland. As the most prestigious global academic event in hematologic malignancies, ICML 2025 brought together over a thousand hematologists, clinical oncologists, radiation oncologists, and translational researchers from around the world. Experts engaged in in-depth discussions on disease mechanisms, translational progress, and clinical innovations in lymphoma.At this year’s meeting, Professor Bouthaina S. Dabaja from MD Anderson Cancer Center delivered a special presentation titled “MD Anderson Updates—New Frontiers in Hematologic Radiation Oncology: Enhancing the Effects of Systemic Therapies.” In an exclusive interview with Oncology Frontier – Hematology Frontier, Professor Dabaja elaborated on evolving principles for radiation use in CAR-T cell bridging therapy, including dose optimization strategies, immune synergy mechanisms, and clinical-to-preclinical breakthroughs. Her insights point toward new directions for precision treatment in hematologic malignancies.
Radiation Therapy in Adoptive Cell Therapy: Strategic Applications and Clinical Experience
Radiation therapy is gaining increasing attention in the context of adoptive cellular therapies, not only as a supportive measure but as a strategy with its own mechanistic contributions. Drawing from over five years of clinical experience at MD Anderson, Professor Dabaja outlined the key principles for integrating radiation into CAR-T cell therapy, emphasizing dose tailoring and toxicity management, and offered a forward-looking view on its synergy with immunotherapy.
1. Radiation as a Bridge to CAR-T: Where, When, and Why
Since MD Anderson adopted CAR-T cell therapy, it has accumulated more than five years of experience in using bridging radiation for diseases including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma, multiple myeloma, and notably, leukemia—which represents one of the most promising areas. Several ongoing prospective studies are investigating not only clinical outcomes but also biomarkers and T-cell phenotypic changes to assess the biological effects of bridging radiation in patients with DLBCL, FL, and myeloma.
2. Unique Sensitivity of Hematologic Malignancies to Radiation
Unlike solid tumors that require curative-intent radiation, hematologic malignancies are intrinsically more sensitive to radiation. Therefore, a lower-dose approach is typically used. This strategy leverages two distinct mechanisms:
- Direct cytotoxicity, and more importantly,
- Immunogenic priming—radiation induces immunogenic cell death, enhancing the overall efficacy of systemic therapies.
3. Field Design: From Localized to Large-Volume Irradiation
While early practice favored localized fields (involved-field or involved-site radiation therapy), emerging data from MD Anderson, Moffitt Cancer Center, and Memorial Sloan Kettering have demonstrated that expanding the radiation field can improve clinical outcomes. However, to mitigate toxicity risks, the dose must be proportionally reduced when larger volumes are irradiated.
4. Balancing Efficacy and Toxicity
Professor Dabaja emphasized that the goal of bridging radiation is not cytoreduction per se, but immune modulation. Even with extended radiation fields, low-dose regimens have not resulted in dose-limiting toxicities or compromised CAR-T efficacy. Bone marrow sparing remains critical, especially in heavily pretreated patients, to avoid exacerbating cytopenias.
In current practice, a differential dosing strategy is commonly used:
- Higher doses (20–30 Gy) for bulky lesions,
- Ultra-low doses (<5 Gy) for disseminated microscopic disease, aiming solely for immune priming.
Recent studies have confirmed that this approach does not increase the incidence of cytokine release syndrome (CRS) or neurotoxicity. A recent Cell publication further demonstrated that 2 Gy whole-body radiation does not produce off-target effects, supporting the immune-synergistic mechanisms of combining radiation with chemo- or immunotherapy.
5. Breakthrough in Preclinical Models: Radiation Boosts CAR-T Potency
One of the most exciting developments, according to Professor Dabaja, stems from preclinical models. In murine models of lymphoma and leukemia, 2 Gy total body irradiation (TBI) significantly enhanced CAR-T cell persistence, proliferation, and anti-tumor efficacy—even when using low-dose CAR-T. This supports the MD Anderson strategy of low-dose, large-field radiation and reflects practices already validated for decades in the hematopoietic stem cell transplant setting.
A randomized controlled trial is now planned at MD Anderson to compare 2 Gy TBI vs. no TBI before CAR-T therapy in acute lymphoblastic leukemia (ALL) patients, with biomarker analysis focused on cytokines, chemokines, and T-cell phenotypes.
6. Expanding to CNS Involvement: The Role of Craniospinal Irradiation (CSI)
As CAR-T therapies become more effective and long-lasting, central nervous system (CNS) relapse rates in leukemia, myeloma, and lymphoma have increased. Given that CAR-T cells can cross the blood-brain barrier and that radiation enhances T-cell fitness (boosting CD8⁺ cytotoxic cells while reducing regulatory T cells), craniospinal irradiation (CSI) is being explored as a preventative strategy for CNS relapse, especially in CNS leukemia patients.
This approach builds on successful historical data from pre-transplant CSI in high-risk CNS leukemia and will be studied in a randomized trial comparing CSI versus no CSI before CAR-T. Immune markers will be collected from both blood and cerebrospinal fluid.
Rethinking Radiation: From a Destructive Tool to a Precision Immunologic Agent
Professor Dabaja emphasized that the role of radiation must evolve—from being viewed as a purely destructive or palliative tool to a precision immunologic enhancer. When combined with modern computer-assisted treatment planning systems, radiation can be delivered precisely, sparing critical structures (heart, lungs, breasts, intestines) while ensuring target coverage.
This technological advancement, combined with its immune-enhancing capabilities, redefines radiation as a “new drug”—now working in synergy not only with CAR-T but also with targeted agents like BTK inhibitors, venetoclax, azacitidine, cyclophosphamide, and brentuximab.
Looking ahead, as allogeneic CAR-T cells, CAR-NK cells, and other cellular therapies become more widely used, radiation—due to its low toxicity and immune-priming potential—is poised to play a pivotal role in safely bridging patients to cellular therapy, particularly those who are chemo-refractory or in earlier treatment stages.
Expert Profile
Professor Bouthaina S. Dabaja
Professor and Chief, Hematologic Radiation Oncology Section
Department of Radiation Oncology, MD Anderson Cancer Center
Dr. Dabaja earned her medical degree from the Lebanese University and completed her residency training at the American University of Beirut and The University of Texas MD Anderson Cancer Center. Since joining MD Anderson in 2006, she has risen through the ranks to become a professor and now leads the hematologic radiation oncology program.
Her clinical work is patient-centered, aiming to maintain high cure rates in lymphoma while minimizing acute and long-term treatment-related toxicities. She is particularly focused on mediastinal lymphomas and has led numerous clinical trials to optimize radiation protocols, offering patients more effective and safer treatment options while reducing long-term complications.
