Lunning Sees Use of Bispecifics in Consolidation Phase in DBLCL

There’s strong evidence to support the use of radiotherapy as consolidation therapy after R-CHOP in diffuse large B-cell lymphoma (DLBCL), but there are limitations as well, Matthew A. Lunning, DO, FACP, professor with the Division of Hematology/Oncology at the University of Nebraska Medical Center in Omaha, explains in a recent interview in Clinical Advances in Hematology & Oncology.¹

Following treatment with the classic combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), he said, radiotherapy is especially indicated in advanced-stage DLBCL with substantial bulk. In early-stage disease, radiotherapy is generally paired with a reduced number of chemotherapy cycles, except for patients meeting FLYER trial criteria, where 4 cycles of R-CHOP proved noninferior to 6 cycles in young, favorable-prognosis patients.² Without radiation access, patients typically need the full 6 cycles of R-CHOP.¹

“We have not been able to prove a benefit with the use of medical oncology agents as consolidation therapy, however,” he said. The ROBUST trial (NCT02285062) showed only a nonsignificant PFS trend with lenalidomide (limited to high-risk patients),³and the GOYA trial (NCT01287741) found no benefit from extending CD20 monoclonal antibody dosing (rituximab or obinutuzumab) beyond induction.⁴

Lunning also pointed out that many global DLBCL trials still use 8-cycle regimens, even though 6 cycles is now the US standard—a mismatch he called unfortunate.

However, he said, radiation still has a major drawback: location, location, location. And that can be hard to overcome, despite improvements in precision that have expanded which sites can be treated. Although Lunning did not address this point, the current upheaval in reimbursement for radiation oncology in the United States may further limit availability of treatment sites.⁵

Will bispecific antibodies advance in frontline use?

Lunning predicted bispecific antibodies will function as an extension of frontline induction therapy rather than true consolidation in most cases. For Lunning, the term “consolidation” has a specific meaning.

“I use that term only when we are using this therapy to improve the depth of remission of patients who are in a metabolic complete response,” he said. “I refer to the old leukemia principles of induction, consolidation, and maintenance as phases of care on a continuum.”¹

Thus, if a patient isn't in complete response after induction, that represents primary treatment failure requiring second-line therapy—not consolidation. He cited the phase 3 STARGLO trial (NCT04408638), which showed glofitamab plus gemcitabine and oxaliplatin (GemOx) improved overall survival versus rituximab-GemOx, but stressed this is second-line, not consolidation, data.⁶

Lunning highlighted 3 ongoing trials testing bispecific antibodies alongside or against R-CHOP or polatuzumab-rituximab-CHP: OLYMPIA-5 (NCT06149286),⁷ SKYGLO (NCT06047080)⁸, and EPCORE DLBCL-2 (NCT05578976)⁹. An advantage of bispecifics is that they appear equally effective in patients with both MYC and BCL2 abnormalities—so-called “double-hit” biology—and non-double-hit patients.

Lunning said EPCORE DLBCL-2 and SKYGLO are the 2 most important randomized phase 3 trials evaluating bispecific antibodies in frontline DLBCL. He described the EPCORE DLBCL-2 design: the trial is enrolling patients with newly diagnosed DLBCL and randomly assigning them to receive either the bispecific antibody epcoritamab (Epkinly, Genmab/AbbVie) combined with R-CHOP, or R-CHOP alone. SKYGLO, meanwhile, is enrolling previously untreated patients with CD20-posi­tive DLBCL and randomizing them to Pola-R-CHP with or without glofitamab (Columvi; Genentech).

Safety considerations and outlook

On adverse events, Lunning identified infection as the most concerning long-term risk with bispecific antibodies, given its potential severity and duration. Cytokine release syndrome is 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 both SKYGLO and EPCORE DLBCL-2 to sharpen 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, applying 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.

References

1. Lunning MA. Could bispecific antibodies be used as consolidation treatment after R-CHOP for DLBCL? Clin Adv Hematol Oncol. 2026;24(5):313-314.

2. Poeschel V, Held G, Ziepert M, et al; for the FLYER Trial Investigators and the German Lym­phoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019;394(10216):2271-2281. doi: 10.1016/S0140-6736(19)33008-9

3. Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39(12):1317-1328. doi: 10.1200/JCO.20.01366

4. Sehn LH, Martelli M, Trněný M, et al. A randomized, open-label, phase III study of obinutuzumab or rituximab plus CHOP in patients with previously un­treated diffuse large B-Cell lymphoma: final analysis of GOYA. J Hematol Oncol. 2020;13(1):71. doi: 10.1186/s13045-020-00900-7

5. Caffrey M. Payers fail to reset radiation oncology payments to match coding changes—and some clinics may close, leading oncologist says. Am J Manag Care. 2026;32(Spec 5):SP221.

6. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024;404(10466):1940-1954. doi:10.1016/S0140-6736(24)01774-4

7. Umberto Vitolo, Lalita Norasetthada, Jae-Cheol Jo, et al. Odronextamab (Odro) plus lenalidomide (+Len) in patients with relapsed/refractory (R/R) follicular lymphoma (FL): First results from part 1 (safety lead-in) of the Phase 3 OLYMPIA-5 study. Blood 2025; 146 (Supplement 1): 5381. doi: 10.1182/blood-2025-5381

8. Ranjana H. Advani, Michael J. Dickinson, Christopher P. Fox, et al. SKYGLO: A global phase III randomized study evaluating glofitamab plus polatuzumab vedotin + rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus Pola-R-CHP in previously untreated patients with large B-cell lymphoma (LBCL). Blood 2024; 144 (Supplement 1): 1718.1. doi:10.1182/blood-2024-194000

9. Sehn LH, Chamuleau M, Lenz G, et al. Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2. J Clin Oncol. 2023;41(suppl 16): TPS7592 doi: 10.1200/JCO.2023.41.16_suppl.TPS7592