Bispecific Antibody Therapy in B-Cell Lymphoma / Lymphoma 08/22/2026

Making a Case for Bispecific Antibody Therapy in B-Cell Lymphoma

Compassionate male healthcare professional wearing white coat and glasses, smiling, with a blurred medical background. Joshua Brody, MD Professional woman with curly brown hair smiling, wearing a dark blazer, in a professional headshot for medical or healthcare context. Sarah Rutherford, MD Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD

Key Points

  • Selecting the optimal treatment for patients with relapsed or refractory B-cell lymphoma can be increasingly complex, particularly when patients are not candidates for chimeric antigen receptor (CAR) T-cell therapy.
  • Bispecific antibodies such as epcoritamab and glofitamab provide additional treatment options for selected patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and can offer outpatient-based treatment approaches, although monitoring and hospitalization may be required during initial dosing.
  • Cytokine release syndrome (CRS) is a common adverse event with T-cell-engaging bispecific antibodies, making appropriate step-up dosing, prophylaxis, monitoring, and patient education essential.
  • Close collaboration between community oncologists and academic centers can help facilitate treatment selection, dosing, toxicity management, and timely escalation of care.

CAR-T and Bispecifics

In this Clinical Insights segment, cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, spoke with Joshua Brody, MD, of Icahn School of Medicine at Mount Sinai, and Sarah Rutherford, MD, of NYU Langone Health, about bispecific antibody options in DLBCL. 

Their key focus included how to determine the optimal course of treatment, how to manage side effects, and the importance of collaboration between community oncologists and academic medical centers.

Standard of Care and Beyond

In the treatment of blood cancers, such as DLBCL, CAR T-cell therapy has been considered the gold standard, according to Dr. Brody. Among many of the clinical trials that have demonstrated this is the phase 3 ZUMA-7 trial, which showed that axicabtagene ciloleucel improved overall survival and event-free survival over standard chemotherapy. However, not all patients are eligible or able to receive CAR-T cell therapy. 

That’s where bispecific antibody therapy can play a pivotal role. The phase 1/2 EPCORE NHL-1 trial demonstrated clinically meaningful response rates with epcoritamab in patients with relapsed or refractory DLBCL, supporting its accelerated FDA approval in this setting.

Unlike chemotherapy regimens, such as GemOx (gemcitabine and oxaliplatin), epcoritamab doesn’t require inpatient hospitalization for observation. The agent is more accessible for community oncologists, Dr. Brody said.

Furthermore, epcoritamab is given as a weekly injection (for the first few months), and can be done in a step-up fashion in an outpatient setting, Dr. Rutherford explained. “This is significant,” she said.“Most of our patients don’t want to go in the hospital even for a 24-hour period.”

Glofitamab, the other FDA-approved bispecific antibody for DLBCL, is administered every 3 weeks. However, the infusion requires an inpatient admission for the first dose, the experts said.

“Bispecific antibodies have changed the field more than any other type of drug for both DLBCL and follicular lymphoma and others,” Dr. Rutherford said. “It’s really exciting.”

Collaboration is Key

Dosing can be a challenge and requires a strong partnership among providers and patients. In Dr. Rutherford’s experience, the most effective strategy has been to do step-up dosing at the hospital, usually about 4 weeks, then transfer to the local physician office. “It’s a good model,” she said. “When you have that close connection with the community and academic settings, we can help guide patients and make sure they get the best care.”

Dr. Brody agreed, urging community physicians to establish relationships—and exchange phone numbers—with physicians at academic organizations. 

The experts also explained the importance of patients’ having a reliable social support system to help manage side effects and identify potential issues.

CRS and PJP Prophylaxis

The most common side effect experienced with T-cell-engaging bispecific antibodies is CRS,  according to Dr. Brody. Grade 2 CRS, which is often seen, is characterized by fever and low blood pressure. CRS risk can be reduced with appropriate step-up dosing, premedication, monitoring, and supportive care, including hydration when clinically appropriate. Having a spouse, relative, or friend reinforce hydration is helpful, Dr. Brody said.

Patients and caregivers also need to be aware of basic guidelines, such as carrying a thermometer at all times, using it frequently, and administering acetaminophen if the temperature exceeds 38°C. Other helpful information that Dr. Brody offers to support teams are criteria for when to take patients to the emergency department. For example, if a patient is feeling dizzy.

Dr. Brody also recommended a course of Pneumocystis jirovecii pneumonia prophylaxis for all patients taking epcoritamab to prevent infections, with dosing more frequent in the first month, then slowly tapering off.

One of the questions that often arises in the community setting, according to Dr. Rohit Gosain, is how to proceed if epcoritamab treatment has paused. And, although it will vary in some cases, the general rule is to restart if it has been more than 6 weeks.

Future of Bispecifics

Based on findings from recent and ongoing trials, Drs. Brody and Rutherford are optimistic about future indications for epcoritamab and other bispecific antibodies in the treatment of DLBCL.

In particular, the EPCORE NHL-2 trial examining the efficacy of epcoritamab in combination with various chemoimmunotherapy regimens, with R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone) for the treatment of B-cell non-Hodgkin lymphomas, could really change the field, Dr. Rutherford said.

Further studies are examining the effectiveness of other bispecifics, such as mosunetuzumab for the treatment of follicular lymphomas, and have achieved significant results. “We’re seeing overall response rates of 80% to 90% and complete response rates of 60% to 70%,” Dr. Rahul Gosain said.

It has become more critical than ever to ensure patients are receiving the appropriate medication and dosage. “I speculate that our own community will continue to see and use more and more bispecific antibodies,” Dr. Rahul Gosain said.