Odronextamab Plus CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma: Matthew Matasar, MD

Despite meaningful progress in the treatment of aggressive B-cell lymphomas, roughly 40% of patients with diffuse large B-cell lymphoma (DLBCL) will relapse or have disease refractory to standard first-line chemoimmunotherapy. For most, the prognosis remains poor even with salvage options.

In this conversation with The American Journal of Managed Care^® (AJMC^®), Matthew Matasar, MD, chief of the Division of Blood Disorders at Rutgers Cancer Institute and professor of medicine at Rutgers Robert Wood Johnson Medical School, discusses results from part 1B of the phase 3 OLYMPIA-3 trial, which evaluated the bispecific antibody odronextamab added to cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (CHOP)–based chemotherapy in higher-risk, newly diagnosed DLBCL. He addresses the rationale for moving this drug class to the front line, the selection of a recommended phase 3 dose, the role of minimal residual disease (MRD), adverse event management in community settings, and the rapidly evolving first-line treatment landscape.

This transcript has been lightly edited for clarity.

AJMC: Could you briefly outline the main results from OLYMPIA-3 part 1B that are particularly important? When you step back and look at the full part 1B data set, what is your overall read on where this treatment modality stands and are you encouraged by what you're seeing?

Matasar: In the OLYMPIA-3 study, we are attempting to determine if adding the CD20 x CD3 bispecific antibody odronextamab (odro) to a standard CHOP-based backbone can improve outcomes in higher-risk newly diagnosed diffuse large B-cell lymphoma. After proving safety, part 1B sought to identify the recommended dose level and schedule for the now-enrolling randomized phase 3 study comparing odro-CHOP to R-CHOP. Our key results here in part 1B were that both the more-intensive and less-intensive dosing strategies yielded high complete response rates, but the less intensive schedule (weekly through cycles 1 and 2, then day 1 of cycles 3 through 6) yielded an equally high MRD-undetectable CR [complete response] rate with less burden of care and fewer adverse events. I’m enthusiastic to help lead the critical randomized component of this trial and hopeful that odro—and the bispecific class more broadly—can be leveraged to cure more people with newly diagnosed aggressive B-cell lymphomas.

AJMC: What gap in diffuse large B-cell lymphoma treatment is this trial designed to address, and why is it needed now?

Matasar: We know that despite advances in the treatment of DLBCL, approximately 40% of patients will relapse or have disease refractory to first-line anthracycline-based chemoimmunotherapy. And despite the availability of novel agents in the treatment of relapsed/refractory DLBCL, including bispecific antibodies and CAR [chimeric antigen receptor] T-cell therapy, the most likely outcome of relapse remains death. Leveraging novel therapies such as odronextamab that are off-the-shelf, scalable, and offer unprecedented activity in this disease to cure more patients with first-line therapy remains the most critical goal for our field.

AJMC: Cytokine release syndrome (CRS) was seen in 55% of patients, though predominantly grade 1. How should community oncologists and their care teams be thinking about CRS monitoring and management protocols in a nonacademic setting, where resources may be more limited?

Matasar: We have encouragingly seen an acceleration in the ability of community oncologists to safely and effectively deliver bispecific antibodies, including management of their predictable toxicity profile, over these last 2 years. Truthfully, grade 1 CRS is an isolated fever that, following treatment with bispecific antibodies undergoing step-up dosing, typically can be abrogated with self-administered corticosteroids. Patient education, staff awareness, and engagement of key stakeholders (intensive care units, emergency rooms, and pharmacists, among others) is critical to the smooth onboarding of bispecific therapy. And there is an increasing awareness that this is not going to remain optional, as the mechanism of action is leveraged not only across B-cell lymphomas, but truly across the full spectrum of malignancy in the months and years to come.

AJMC: Adverse events led to dose interruption or delay in 70% of R1 patients vs 50% in R2—yet no Odro dose reductions occurred. What does that tell us about the manageability of this regimen, and how does it compare to what we see with other bispecific antibody combinations?

Matasar: We do need to be very attentive to avoid treatment interruption with the anthracycline backbone in chemoimmunotherapy programs treating newly diagnosed DLBCL. We have seen in prior studies that when adjunctive therapies reduce dose-density of the CHOP component of therapy, that benefit of the additional treatment is negatively offset by such reductions. The part 2 team is working to streamline toxicity assessment and grading to ensure that we avoid treatment reduction or interruption when not absolutely necessary on clinical grounds.

AJMC: R2, the less frequent dosing schedule, was selected as the recommended phase 3 dose. From a value and access standpoint, what does a less frequent administration schedule mean for patients and payers in terms of infusion center burden and total cost of care?

Matasar: We clearly need to be cognizant, in our design and conduct of research, of the need to position the patient's journey at the center of the conversation. Yes, factors of resource utilization and cost-effectiveness are important, but we seek in the conduct of trials these opportunities to align all of these related priorities. Thankfully, the data from part 1B support a treatment schedule that is less burdensome to patients [and] places less pressure on physical and fiscal resources without compromising our mission of curing this disease.

AJMC: Bispecific antibodies are increasingly moving into the frontline setting across B-cell malignancies. How do you see odro-CHOP fitting into a crowded first-line DLBCL landscape that may soon include other novel combinations?

Matasar: We may indeed soon be facing an embarrassment of riches. We already have pola-RCHP, which improves progression-free survival [PFS] modestly but significantly, and with no significant toxicity trade-offs. We have frontMIND about to be presented at ASCO, although we have a press release reporting PFS without OS [overall survival] benefit; here we anticipate increased toxicity from adding tafasitamab and lenalidomide to an R-CHOP backbone and await granular data of risk and benefit for this approach, including subset analyses. And we have many other potentially practice-changing protocols that have ongoing accrual or have completed accrual, including studies evaluating sister drugs to odronextamab—glofitamab and epcoritamab—being added to Pola-RCHP or R-CHOP, respectively; acalabrutinib being added to R-CHOP in activated B-cell subtype DLBCL; and golcadamide being added to R-CHOP. And this is to say nothing of novel consolidative strategies such as leveraging CAR T-cell therapy for high-risk disease or as preemptive therapy for MRD positivity following first-line therapy. My expectation, my hope, is that we will have a fragmented landscape littered with positive trials, giving clinicians new tools to personalize care and optimize outcomes.

Reference

Matasar M, Jandel A, Assi R, et al. First-line odronextamab (Odro) plus chemotherapy (CHOP) in diffuse large B-cell lymphoma (DLBCL): OLYMPIA-3 Part 1B results. J Clin Oncol 2026; 44 (suppl 16) abstr 7009. doi: 10.1200/JCO.2026.44.16_suppl.7009