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FAQs: Bispecific Antibodies for R/R DLBCL
Optimizing Bispecific Antibody Therapy for R/R DLBCL: Answers to Frequently Asked Questions

Released: October 18, 2024

Expiration: October 17, 2025

Sherry Adkins
Sherry Adkins, MSN, ANP-C, FAAN
Kathleen Dorritie
Kathleen Dorritie, MD
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Key Takeaways
  • Bispecific antibodies are a new therapy option for patients with relapsed or refractory diffuse large B-cell lymphoma, offering advantages over CAR T-cell therapy, including lower toxicity risks, shorter hospital stays, and “off-the-shelf” availability.
  • Step-up dosing for bispecific antibodies is typically initiated at specialized centers experienced in managing cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), but after this phase patients can safely continue treatment at their local community oncology site.
  • Proper education for patients and caregivers on CRS and ICANS, including close monitoring and when and where to seek healthcare professional support is essential.

Bispecific antibody therapies are a recent new option for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In this commentary, we share our answers to frequently asked questions posed by a live audience of healthcare professionals during a webinar covering the latest in the use of bispecific antibody therapy for patients with R/R DLBCL, including current management of their associated adverse events (AEs).

What are the most common concerns expressed by patients with R/R DLBCL receiving bispecific antibody therapy and their family members, during your discussions with them?

Sherry Adkins, MSN, ANP-C, FAAN:
Patients often express concerns about the potential for AEs with anti–CD3xCD20-directed bispecific antibodies, particularly those who have previously undergone chimeric antigen receptor (CAR) T-cell therapy and experienced AEs including immune effector cell–associated neurotoxicity syndrome (ICANS). In addition, most patients express interest in the possibility of receiving treatment with their local oncologist, because extended stays at a hospital away from their home are often impractical for most people. Patients also seek information on available resources to support them if family members are not nearby during the step-up dosing required with glofitamab (hospitalization recommended for 24 hours after step-up dose 1 and if cytokine release syndrome [CRS] with prior dose) and epcoritamab (hospitalization recommended for 24 hours after cycle 1 Day 15 dose). Some patients ask about duration of treatment. For example, glofitamab has a fixed 12-cycle dosing regimen, with 1 dose every 21 days after initial step-up dosing after a single obinutuzumab pretreatment. By contrast, epcoritamab does not require obinutuzumab for tumor debulking and is administered subcutaneously. Its dosing is more frequent, and patients responding to treatment can continue after the first 12 cycles.

Kathleen Dorritie, MD:
I agree with Ms Atkins and I would also say that in my experience, patients who have undergone CAR T-cell therapy are particularly motivated, as bispecific antibody therapy represents a more definitive treatment compared to other available therapies for R/R DLBCL. These conversations highlight why it is so important that these novel treatments are offered at community healthcare sites. Relative to my institution, some of these community oncology sites are located 2 to 3 hours away, which poses practical challenges for outpatient step-up dosing due to potential delays in managing toxicities. However, initial step-up dosing is managed centrally with ongoing efforts to establish additional supportive infrastructure at community oncology treatment sites.

How does the care team decide which bispecific antibody is best suited for each patient?

Kathleen Dorritie, MD:
The safety and efficacy profiles for the 2 FDA-approved anti–CD3xCD20-directed bispecific antibodies epcoritamab and glofitamab were found to be similar in pivotal trials. Regarding response rates, epcoritamab yields an overall response rate of 63% and glofitamab of approximately 52%, but both show a complete response rate of approximately 39%. Regarding safety, grade 3 CRS with either was reported at approximately 3%, and grade 3 ICANS was 3% with glofitamab and 0% with epcoritamab. Because these data are so similar, it can be challenging for clinicians to choose between the 2 approved agents. Although some of these bispecific antibodies—epcoritamab, glofitamab, and odronextamab—do have slight structural differences, such as differences in mode of cell targeting and killing, which may impact their cytotoxic potential. By contrast, we have not seen major differences in safety or efficacy profiles. As a result, the decision often depends on practical factors such as administration, dosing frequency, and whether patients prefer a time-limited treatment or longer-term therapy.

How do these therapies compare to other available options?

Kathleen Dorritie, MD:
A significant advantage of anti–CD3xCD20-directed bispecific antibodies is their “off-the-shelf” availability, allowing for immediate use, compared to CAR T-cell therapies, which require manufacturing time and other logistical considerations before treatment can begin.

The safety profiles of bispecific antibodies demonstrate lower toxicity, particularly with a reduced risk of CRS and lower neurologic toxicity risks compared to CAR T-cell therapies. This makes them a good option for patients who are not suitable candidates for CAR T-cell therapy due to comorbidities or other factors. In addition, hospitalization times are much shorter with bispecific antibodies.

Another key difference is the target of these therapies. CD20-directed bispecific antibodies are very different from CD19-directed CAR T-cell therapies still in development. CD19-directed therapies would target the same antigen in patients who have already undergone CAR T-cell therapy. However, prior CAR T-cell therapy does not exclude the use of bispecific antibodies, and vice versa, giving both patients and providers more flexibility.

In general, bispecific antibodies have shown improved efficacy and a likely better safety profile compared to traditional salvage chemotherapy regimens which we believe will lead to improved quality of life for patients as well.

Sherry Adkins, MSN, ANP-C, FAAN:
I would like to echo what Dr Dorritie mentioned regarding the necessity of administering the initial step-up doses of bispecific antibodies at specialized centers. Although the risk of severe AEs, such as CRS and ICANS is lower compared to CAR T-cell therapies, these toxicities still warrant careful monitoring. Once the step-up dosing phase has been completed, patients should be able to continue treatment at their local community oncology site.

The main AEs we are concerned about for this group of patients being treated with bispecific antibodies are CRS and ICANS, but also cytopenia, hypogammaglobulinemia, and an increased risk of infections. CRS and ICANS that occur in patients receiving bispecific antibodies are graded according to the American Society of Transplantation and Cellular Therapy Consensus Grading, developed in 2019 for CAR T-cell therapies. Accurate grading is very important, as the grade of toxicity determines the treatment strategy. The incidence and timing of CRS varies by product. Overall, 40% to 65% of patients experience CRS, with most cases being grade 1 or 2. Grade 3 and 4 toxicities are only seen in 2% to 4% of patients, which is a favorable outcome. Neurotoxicity is also rare, affecting 1% to 8% of patients, depending on the product.

Cytopenia, particularly neutropenia, occurs in 25% to 35% of patients, which increases the risk of infections. Although less common, tumor flare reactions are another potential concern, especially for patients with bulky disease in areas like the neck or mediastinum. It is important to monitor for a possible tumor flare and consider preemptive measures before initiating bispecific antibody therapy again. In addition, hypersensitivity reactions can occur, although these are often managed with premedications such as steroids, antihistamines, and acetaminophen.

What practical challenges or issues have you seen with incorporating bispecific antibodies into practice?

One of the main challenges we face with these novel bispecific therapies is ensuring that all members of the healthcare team are appropriately educated on how these drugs work, as well as toxicity grading and management.

Another important consideration is the financial burden on both the facility and the patient. Deciding whether these patients are better off inpatient or outpatient depends on available resources, and centers need to evaluate which option is more cost-effective. Patients from “out of town” may need help with financial assistance for travel, lodging, and meals. Many pharmaceutical companies offer financial assistance, organization such as the Leukemia & Lymphoma Society can provide patients with additional support, and social workers can connect patients with identifying resources.

What do you recommend as key points and resources to educate patients about?

It is really important that both the patient and any accompanying caregiver receive thorough education regarding the signs and symptoms of CRS and neurotoxicity, as well as clear instructions on appropriate actions to take should these complications arise. This could include contacting their primary healthcare professional or, depending on the situation, presenting directly to the emergency room. The specific protocol will vary based on patient’s individual needs.

For patients undergoing at-home monitoring, it is essential that they have a thermometer so they are able to regularly check their temperature. The consensus guidelines recommend taking the temperature 3 times a day for 2 days following the step-up doses, alongside monitoring for signs of neurotoxicity. Some institutions may instruct family members to monitor the ICE score to access neurotoxicity; however, in most cases, caregivers are advised to monitor for indicators such as confusion, changes in speech, difficulty staying awake, seizures, or any unusual behavior.

In addition, it’s important to provide patients with a wallet card that contains information about the specific treatment they received and the risks of developing CRS and ICANS. This card can be invaluable if the patient goes to another emergency room that’s unfamiliar with this medication. We encourage patients to take a picture of the wallet card and store it on their smartphone for easy access, though they can carry a paper copy also.

Your Thoughts?
Have you provided care for patients with R/R DLBCL who are being treated with bispecific antibody therapy? What has been your experience with these patients so far in your practice? Download the slides from the live program and join the conversation by answering the polling question and posting a comment.

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How often are you discussing bispecific antibodies as a treatment option with your patients with R/R DLBCL?

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