Radiotherapy remains a strong option for consolidation therapy in diffuse large B-cell lymphoma (DLBCL) following R-CHOP treatment, but its use comes with specific limitations. Matthew A. Lunning, DO, FACP, a professor in the Division of Hematology/Oncology at the University of Nebraska Medical Center, outlined the current evidence and emerging alternatives in a recent interview published in Clinical Advances in Hematology & Oncology.
For patients with advanced-stage DLBCL and substantial bulk, radiotherapy is often indicated after the standard combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. In early-stage disease, doctors typically combine radiation with a reduced number of chemotherapy cycles. However, patients who meet the criteria from the FLYER trial may receive only 4 cycles of R-CHOP, a method that proved noninferior to 6 cycles in young, favorable-prognosis patients. Without access to radiation, patients generally require the full 6 cycles.
Lunning noted that medical oncology agents have so far failed to prove effective as consolidation therapy. The ROBUST trial showed only a nonsignificant progression-free survival trend with lenalidomide, limiting its use to high-risk patients. Similarly, the GOYA trial found no benefit from extending CD20 monoclonal antibody dosing with rituximab or obinutuzumab beyond the induction phase.
Despite the data supporting radiotherapy, Lunning highlighted a persistent drawback: location. Access to treatment sites remains a significant hurdle, described as a matter of “location, location, location,” even as precision improvements have expanded the types of sites that can be treated. He also observed that current upheaval in reimbursement for radiation oncology in the United States may further limit availability. Lunning also pointed out that many global DLBCL trials still use 8-cycle regimens, even though 6 cycles is now the US standard, which is a mismatch he described as being unfortunate.
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The Definition of Consolidation
Lunning offered a specific definition for consolidation, arguing the term should only apply when therapy is used to improve the depth of remission in patients who are already in a metabolic complete response. He draws a clear line between consolidation and second-line therapy, referring to the old leukemia principles of induction, consolidation, and maintenance as phases of care on a continuum. If a patient is not in complete response after induction, he views that as primary treatment failure requiring a new approach rather than an additional step in the initial care plan. To illustrate this distinction, he cited the phase 3 STARGLO trial, which showed glofitamab plus gemcitabine and oxaliplatin improved overall survival versus rituximab-GemOx, emphasizing that this data represents second-line treatment, not consolidation.
Looking toward future therapies, Lunning predicted that bispecific antibodies will likely function as an extension of frontline induction therapy rather than true consolidation in most cases. A significant advantage of bispecifics is that they appear equally effective in patients with both MYC and BCL2 abnormalities—known as “double-hit” biology—and non-double-hit patients. He identified three ongoing trials testing these agents alongside or against R-CHOP or polatuzumab-rituximab-CHP: OLYMPIA-5, SKYGLO, and EPCORE DLBCL-2.
Lunning described EPCORE DLBCL-2 and SKYGLO as the two most important randomized phase 3 trials evaluating bispecific antibodies in frontline DLBCL. The EPCORE DLBCL-2 trial is enrolling patients with newly diagnosed DLBCL, randomizing them to receive the bispecific antibody epcoritamab combined with R-CHOP or R-CHOP alone. Meanwhile, SKYGLO is enrolling previously untreated patients with CD20-positive DLBCL and randomizing them to Pola-R-CHP with or without glofitamab.
Regarding safety, Lunning identified infection as the most concerning long-term risk associated with bispecific antibodies due to its potential severity and duration. Cytokine release syndrome remains the primary shorter-term concern, though he noted it appears less frequent when the bispecific agent is introduced later in a treatment sequence. He expects the results from SKYGLO and EPCORE DLBCL-2 to sharpen the understanding of this risk profile. Looking ahead, he argued that if bispecifics are eventually validated as true consolidation therapy, their value will likely be concentrated in specific patient subtypes using a risk-adapted approach. Patients already cured after 6 cycles, he said, gain no benefit from a seventh, eighth, ninth, or tenth dose—only added toxicity—reinforcing his view that consolidation should be reserved for patients who need deeper remission rather than applied universally after cure is achieved.
