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Bispecific Antibodies in NHL
Insights from HOPA 2025: Incorporating Bispecific Antibodies Into NHL Management

Released: June 26, 2025

Expiration: June 25, 2026

C. Brooke Adams
C. Brooke Adams, PharmD, BCOP
Sarah Profitt
Sarah Profitt, PharmD, BCOP
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Key Takeaways
  • Bispecific antibodies (BsAbs) provide high response rates in relapsed/refractory DLBCL and follicular lymphoma, with off-the-shelf availability, outpatient administration, and manageable toxicity profiles, making them practical for both academic and community settings.
  • Key considerations for choosing among BsAbs include route of administration (SC vs IV), duration (fixed vs indefinite), steroid burden (eg, high dexamethasone use), and clinic logistics.
  • To effectively manage cytokine-release syndrome (CRS) and ICANS and ensure safe use of BsAbs, institutions use CRS grading, ICE scoring, EMR flags, and pretreatment education. Most grade 1 CRS events can be handled in an outpatient setting with proper supportive care and infrastructure to avoid hospital admissions.

We have seen firsthand how bispecific antibodies (BsAbs) are changing the treatment paradigm for patients with hematologic malignancies like diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In patients with relapsed non-Hodgkin lymphoma (NHL), BsAbs provide high response rates along with favorable safety profiles. In addition, they offer an off-the-shelf alternative to CAR T-cell therapy as well as more accessible outpatient administration. Through trials like EPCORE NHL-1, NP30179, GO29781, and ELM-2, we are gaining a better understanding of CD20-directed bispecific agents’ place in the treatment landscape, including epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Equally important to understanding the efficacy with these agents is understanding the protocols and workflows we’ve developed to manage adverse events (AEs)—particularly cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS)—to empower pharmacists and care teams to integrate these agents effectively into clinical practice.

Considerations When Recommending BsAbs for Patients With DLBCL

Brooke Adams, PharmD, BCOP:
There are currently 2 FDA-approved BsAb therapies for patients with DLBCL—epcoritamab and glofitamab. Epcoritamab was FDA approved on May 19, 2023, for patients with relapsed or refractory (R/R) DLBCL, not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after 2 or more lines of systemic therapy. Epcoritamab quickly became adopted at our center once it was FDA approved. In EPCORE NHL-1, a 63% overall response rate (ORR) was reported, with 40% complete response (CR), in patients with R/R DLBCL who were treated with epcoritamab after 2 or more prior therapies—including those post CAR T-cell therapy.

Epcoritamab is administered subcutaneously (SC), with step-up dosing to increase tolerability and help mitigate the potential for CRS. It is a patient-friendly option that can generally be administered in the outpatient setting. However, it is currently recommended in the prescribing information that patients with DLBCL or high-grade B-cell lymphoma be hospitalized for 24 hours after administration of the first full dose of epcoritamab (cycle 1 Day 15 dosage of 48 mg). With appropriate infrastructure at the health system to monitor for and manage CRS outpatient, many institutions have successfully avoided routine hospitalization for monitoring. The convenience of SC administration and ability to move to monthly dosing after cycle 10 are major advantages with epcoritamab. Nevertheless, we must also be mindful of the required steroid pulse (16 mg dexamethasone 4 days per week initially), which can pose a challenge for patients with poorly controlled diabetes or mood disorders and is an indefinite treatment at this time.

Sarah Profitt, PharmD, BCOP:
Glofitamab was FDA approved just weeks after epcoritamab, on June 15, 2023, for patients with R/R DLBCL, NOS, or large B-cell lymphoma (LBCL) arising from FL after 2 or more lines of systemic therapy. Although similar in efficacy (ORR and CR approximately 52% and 40%, respectively) to epcoritamab, the IV route of administration, pretreatment with obinutuzumab for disease control to help mitigate CRS, and fixed 12-cycle duration set glofitamab apart from epcoritamab.

At Vanderbilt, we prioritize epcoritamab when feasible because of patient convenience with SC dosing, but our clinic infrastructure supports administration of either epcoritamab or glofitamab. Our outpatient bispecific clinic allows us to safely manage 4-hour infusions for glofitamab as needed. Our practice prefers glofitamab in select scenarios, especially in patients who can’t tolerate high-dose steroids, who want a fixed-duration regimen, or when we are combining BsAbs with chemotherapy.

For example, in the recent STARGLO and EPCORE NHL-2 trials, both glofitamab and epcoritamab have shown promising activity when combined with GemOx and have been adopted into NCCN guidelines. The phase III STARGLO trial reported a significant improvement in overall survival (OS) with glofitamab plus GemOx (median OS not reached after a median follow-up of 24.7 months) vs rituximab plus GemOx (median OS of 13.5 months) in R/R DLBCL after 1 or more previous line of therapy, although in 2025 the FDA stated STARGLO data was not applicable to patients in the United States with DLBCL since only 9% of the enrolled patients were from the US. The phase I/II EPCORE NHL-2 reported an ORR of 80% and a median OS of 21.6 months combining epcoritamab with GemOx. Also listed in the NCCN guidelines for treatment of R/R DLBCL is the combination of polatuzumab + mosunetuzumab, based on a phase Ib/II trial.

Brooke Adams, PharmD, BCOP:
At Orlando Health, we’ve taken a similar approach when considering either epcoritamab or glofitamab for patients with R/R DLBCL. Our decision comes down to patient-specific factors—performance status, comorbidities, prior lines of therapy, preference for fixed vs indefinite therapy, and clinic logistics. However, both of these BsAbs are reasonable treatment options to consider for these patients. A number of novel antibody–drug conjugate and bispecific combinations are currently in clinical trials with promising results, none of which have been FDA approved at this time.

BsAbs for Patients With FL

Brooke Adams, PharmD, BCOP:
For our patients with R/R FL, mosunetuzumab has been a valuable addition. Mosunetuzumab was granted accelerated approval by the FDA in December 2022 for treatment of adult patients with R/R FL after 2 or more lines of systemic therapy. It is an IV agent administered over a fixed duration of 8 cycles for patients who achieve a CR, or therapy can extend up to 17 total cycles for patients with a partial response to the initial 8 cycles. In GO29781, the ORR with mosunetuzumab was 80% in patients with R/R FL, with 60% achieving CRs. Of importance, there was minimal grade 3 or higher CRS, and the treatment is outpatient-friendly with no hospitalization recommended per prescribing information.

Sarah Profitt, PharmD, BCOP:
Epcoritamab is also a treatment option in R/R FL, especially when we want an SC, indefinite option. Currently available under FDA accelerated approval for use in adults with R/R FL after 2 or more lines of systemic therapy, epcoritamab maintains high efficacy—82% ORR and 62.5% CR—but adds a third step-up dose (3 mg on Day 15) to reduce CRS risk and support outpatient administration. Like the treatment decision in DLBCL, choosing between these 2 FDA-approved options for patients with FL includes consideration of patient comorbidities, preference for fixed vs indefinite therapy, and clinic logistics.

Brooke Adams, PharmD, BCOP:
Odronextamab is currently under FDA review with a potential decision on approval for patients with R/R FL after 2 or more lines of systemic therapy in July 2025. Odronextamab demonstrated an 80% ORR and 73% CR in patients with R/R FL, but its use is more complex in terms of dosing and monitoring due to a higher rate of CRS (any grade: 56%) and neutropenia (any grade, treatment-related: 30.5%) compared with other CD20-directed BsAbs. If approved this summer in 2025, it will be another tool, but likely reserved for select patients given the safety profile.

Addressing Toxicity Management With BsAbs: CRS, ICANS, and Beyond

Sarah Profitt, PharmD, BCOP:
When discussing considerations for BsAbs with patients, I think it is helpful to give a sense of the timeline of potential AEs that are associated with these agents. I explain to patients what AEs they may experience immediately after beginning treatment or within a few days or weeks of administration vs what AEs may be expected a few months into treatment. CRS and ICANS are the major acute AEs to consider, but we can manage them successfully with well-defined protocols. CRS is an overactivation of the immune system that leads to progressive symptoms including fever at the onset and a variety of other clinical manifestations like hypotension, capillary leak, hypoxia, and even end organ dysfunction.

The 2019 American Society for Transplantation and Cellular Therapy consensus grading criteria guides our approach. For grade 1 CRS, categorized by a fever of ≥38°C, current guidelines recommend acetaminophen, oral hydration, and close monitoring. However, at my institution we do not rely on acetaminophen alone. Instead, we provide patients with a prescription for 2 doses of 8-10 mg dexamethasone to take as needed. As part of our patient education, they are instructed to immediately call our on-call provider, with 24/7 support, if they experience a fever and take 1 dose of their dexamethasone. Then, we may have them come into our clinic if it is during the day or to the ER if it is overnight if additional in-person monitoring is needed.

Brooke Adams, PharmD, BCOP:
We do the same. Our patients receive a prescription for 10 mg dexamethasone with “as-needed” instructions. If they spike a fever, they call the on-call provider immediately. Most resolve without ER visits or admission. The key is empowering patients with education upfront. For grade 2 CRS, we recommend inpatient management, considering treatment with anticytokine therapy with tocilizumab for support. For grade 3 CRS, we recommend inpatient management and consider intensive care unit or a higher level of care due to the supportive care needs such as vasopressors or ventilatory support, if needed, for hypoxia in addition to tocilizumab and dexamethasone.

Sarah Profitt, PharmD, BCOP:
ICANS has been well described in the literature for CAR T-cell therapy and now for BsAb treatment. The most common symptoms with ICANS include difficulty finding words, mild tremors, difficulty with expressive speech, and being able to name an object in the room. We use immune effector cell–associated encephalopathy scores to monitor for ICANS, especially early in treatment. We’ve embedded these tools into our electronic health records (EHR) and use chart flags so emergency departments and cross-coverage teams know if a patient is on a BsAb. This simple incorporation into the EHR can make a big impact on the care and overall outcomes for patients on these types of treatments.

Brooke Adams, PharmD, BCOP:
I agree, integration of this information in patients’ EHR has helped our nurses and providers grade toxicities quickly and flag patients across our regional hospitals who are receiving BsAbs and may experience treatment-related AEs. We also educate patients on which EDs to go to in case of symptoms—especially those where our system alerts are active.

Sarah Profitt, PharmD, BCOP:
Important delayed toxicities that patients should be aware of include hematologic AEs, specifically neutropenia and infections, as these often show up months into BsAb therapy. With the late emergence of grade 3 neutropenia and the potential for infections, we generally recommend prophylaxis against herpes virus and pneumocystis jirovecii pneumonia when initiating BsAb therapy as well as IVIG for patients with IgG <400 or with recurrent infections. We’re not routinely giving antibacterial or antifungal prophylaxis, but G-CSF support and additional antimicrobial prophylaxis can be used when needed.

Conclusion: What This Means for Clinical Practice

Brooke Adams, PharmD, BCOP:
BsAbs have transformed how we approach treatment decisions for patients with R/R NHL. The choice is no longer just about efficacy but also about personalizing care by matching the right therapy to the right patient in the right setting.

Sarah Profitt, PharmD, BCOP:
As pharmacists and clinicians, we play a pivotal role. From selecting agents, building protocols, educating patients, and managing toxicity, we are the front line in bringing these therapies to life. With more agents and combinations on the horizon, we must stay engaged, adaptive, and ready to guide care forward.

Have you provided care for patients with NHL who are being treated with a BsAb therapy? What has your experience with these patients so far been 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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