New Therapies and Playbooks as Bispecifics Expand in Lymphoma Care

At the 2026 Community Oncology Alliance Annual Meeting in Orlando, Florida, experts explored the rapid evolution of bispecific T-cell engager therapies (BTCEs) and the operational realities shaping their use in clinical practice for patients with lymphoma. As these agents move earlier in the treatment paradigm and into a broader range of care settings, oncology teams are being challenged to adapt workflows, standardize safety protocols, and build the infrastructure needed to support their safe and scalable delivery.

The discussion highlighted both the clinical nuances of BTCEs as well as the critical role of multidisciplinary coordination when translating these therapies from controlled trial settings into real-world oncology practice.

What BTCEs Are and How They Work

BTCEs are antibodies consisting of 2 different binding arms. One arm binds to a tumor antigen whereas the other binds to CD3 on T cells, physically linking them to activate the T cells and trigger targeted cytotoxicity against malignant B cells. In B-cell lymphoma, CD20 is the primary tumor antigen used for these products.

FDA approvals for this drug class accelerated significantly starting in 2022. Mosunetuzumab (Lunsumio; Genentech) was among the first to receive approval, initially as an intravenous (IV) formulation in follicular lymphoma before later gaining a subcutaneous option. Additional approvals followed across both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Notably, bispecifics are moving earlier in the treatment paradigm at a rapid pace, with first-line indications anticipated in the near future—a shift that will meaningfully expand the population of patients eligible for these therapies.

Despite belonging to the same mechanistic class, these agents cannot be treated as interchangeable from a workflow or operational standpoint. They differ in route of administration, with some given via IV and others subcutaneously, and step-up dosing schedules vary by product. Premedication and prophylaxis strategies also differ significantly: one agent requires CD20 monoclonal antibody debulking with obinutuzumab (Gazyva; Genentech) 7 to 14 days prior to the bispecific in order to reduce tumor burden, whereas another requires 3 days of dexamethasone following each dose, resulting in considerable cumulative steroid exposure.

Even the cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) profiles vary—IV formulations tend to produce a faster onset of CRS, while subcutaneous formulations have a slower, more delayed onset that calls for a different monitoring window. This degree of product-to-product variability is precisely why standardized operating procedures and individualized treatment plans are essential when working with this drug class.

Safety and Adverse Event Management With BTCEs

Although CRS and ICANS tend to dominate discussions around BTCEs, these toxicities are generally short-term and manageable. The more significant long-term concern is infection risk. Once the step-up dosing period—which typically lasts less than a month—is complete, clinical attention should shift toward infections as the primary cause of serious harm, alongside hypogammaglobulinemia and cytopenias reflecting ongoing immune suppression.

“We can spend half of our presentations talking about CRS and ICANS, but this is not the biggest concern,” Brooke Adams, PharmD, BCOP, a clinical pharmacist specializing in stem cell transplant and cellular therapy at the Orlando Health Cancer Institute in Orlando Florida, said during the session. “We need to be worried about infections… this is where we really need to spend the majority of our efforts, keeping these patients alive on these very sexy therapies.”

CRS

CRS is an expected and typically mild occurrence with bispecific T cell engagers. The vast majority of cases are grade 1 or 2, with grade 3 or 4 events being rare in experienced practices. To put grade 1 CRS in accessible terms: a simple fever managed with acetaminophen or ibuprofen meets the definition—something clinicians already handle routinely. Early signs to watch for include fever and tachycardia; if not addressed promptly, these can progress to hypoxia, leaky lungs, and hypotension. Other symptoms not captured in formal CRS grading scales—such as transaminitis, fatigue, headache, and myalgias—may also occur as a result of systemic cytokine activity. Grading follows the ASTCT 2019 consensus criteria, based on fever, blood pressure, and oxygen requirements.

For low-grade CRS managed at home or in the clinic, antipyretics are the first step. A practical approach used by some teams is a "dex in pocket" strategy—prescribing dexamethasone to all bispecific patients in advance so that if symptoms develop at home, particularly when a patient may be traveling to a care setting, early intervention is possible without delay. For higher-grade CRS, dexamethasone is the primary workhorse, with tocilizumab added selectively based on severity and the specific product being used. Clear standard operating procedures (SOPs) define when to escalate from clinic to the emergency department to inpatient admission, as well as dosing and criteria for each intervention.

ICANS

ICANS is uncommon with bispecific T cell engagers, occurring in fewer than 5% of patients in experienced practices, and when it does occur, it tends to be low grade. This stands in notable contrast to the higher frequency and severity seen with CAR-T therapy. Mild presentations may involve subtle mental status changes, while more severe cases can include agitation, marked confusion, and somnolence. Seizures and coma represent rare but serious extremes.

Grading is linked to the ICE score and level of arousal: grade 1 corresponds to mild confusion with an ICE score of 7 to 9; grade 2 to more significant obtundation with a score of 3 to 6; and grades 3 and 4 reflect scores of 0 to 2 with progressively diminished response to stimuli. Imaging with CT and EEG should be considered when there is clinical concern, and early neurology involvement is encouraged. Dexamethasone is again the mainstay of treatment, and some clinicians add levetiracetam (Keppra; UCB Pharmaceuticals) at grade 2 or higher—ahead of what some guidelines specify—to reduce the risk of progression to seizures.

SOPs, EMR Infrastructure, and Workflow

Pharmacists play a leading role in building the SOPs that govern adverse event (AE) management for bispecific therapies. These protocols draw on both label recommendations and local clinical experience, and cover CRS and ICANS grading, infusion management decisions, premedication adjustments for subsequent doses, and escalation pathways. Separate SOPs exist for infusion and clinic staff on one hand and triage nurses on the other, ensuring that after-hours calls and at-home events are handled through the right channels rather than falling into standard queues.

EMR infrastructure reinforces these protocols at every touchpoint. In the emergency department, best practice alerts flag patients receiving bispecific agents and prompt clinicians to either confirm that CRS is not a concern or activate a linked order set. Nursing flowsheets for CRS and ICE assessments auto-populate provider notes to standardize documentation.

Practice Settings and Models for Bispecifics

BTCEs are being implemented across a spectrum of oncology practice settings, each with distinct operational capabilities and constraints. At one end are fully integrated clinics embedded within hospital systems. These environments offer seamless access to inpatient units, observation services, emergency departments, intensive care units, and subspecialists. This level of integration enables rapid escalation of care when needed. For example, a patient experiencing complications overnight can be directly admitted without delay. These settings were particularly valuable during early BTCE adoption, allowing clinicians to initiate step-up dosing in the inpatient setting and then transition patients to outpatient care once they were stable.

Partially integrated clinics occupy a middle ground. These practices share certain resources or clinical pathways with a hospital system but maintain largely independent workflows. While they may benefit from access to select hospital-based services, they do not operate with the same immediacy or level of coordination as fully integrated systems. As a result, care delivery often requires more deliberate planning and coordination, particularly when escalation or inpatient monitoring is needed.

At the other end of the spectrum are non-integrated, independent community practices. These clinics have no formal hospital affiliation or ownership structure, though they often maintain collaborative relationships with local hospitals or academic centers. In these settings, BTCE step-up dosing can still be delivered in the outpatient setting through highly structured protocols and workflows. However, because they lack direct admitting privileges, patients who are not appropriate for outpatient management must be referred externally for higher-acuity care.

Across these settings, 3 primary models for delivering BTCE step-up dosing have emerged. The earliest and most conservative approach is the inpatient model, which was commonly adopted by academic medical centers and large community hospitals during initial implementation. In this model, step-up doses are administered in the hospital, where patients can be closely monitored for AEs such as CRS and ICANS. Once patients complete the step-up phase and are clinically stable, they are discharged to continue treatment in the outpatient setting.

A hybrid model has since developed as a bridge between inpatient and outpatient care. In this approach, BTCEs are administered in the outpatient clinic, but patients are subsequently monitored in an observation unit or inpatient setting. This model allows institutions to maintain outpatient billing for drug administration while still providing a higher level of monitoring. It also helps mitigate some of the logistical and financial complexities associated with full inpatient admission, unless clinical circumstances—such as extended monitoring needs—trigger inpatient criteria.

The fully outpatient model is increasingly viewed as the target state for BTCE delivery, particularly as experience and comfort with these therapies grow. In this model, both step-up dosing and monitoring occur entirely in the outpatient setting. Successful implementation depends on rigorous patient selection, including assessment of performance status, comorbidities, proximity to care, and availability of caregiver support. It also requires comprehensive patient and caregiver education, access to home monitoring tools such as blood pressure cuffs and thermometers, and clearly defined protocols for triage and escalation of care. Practices utilizing this model often reserve it for patients who meet strict eligibility criteria, while directing higher-risk individuals to hybrid or inpatient pathways.

The Pharmacist’s Role

Pharmacists play a central role in designing and sustaining the operational framework required to safely deliver BTCEs. A core responsibility is the development and ongoing maintenance of SOPs that ensure consistency, safety, and scalability. Importantly, these protocols are not static; they evolve continuously based on both manufacturer guidance and real-world clinical experience, requiring regular updates as new data and patterns emerge.

Beyond protocol development, pharmacists are instrumental in translating these SOPs into functional tools within the EMR. This includes building alerts and best-practice advisories that flag BTCE patients in high-risk settings (eg, emergency department) to ensure that clinicians can quickly access appropriate management pathways. In the outpatient setting, safeguards are embedded to prevent unintended changes to treatment plans without proper oversight.

Pharmacists also serve as operational leaders, helping to define how BTCE therapies are implemented across different care models. They contribute to the design of inpatient, hybrid, and fully outpatient step-up dosing strategies, tailoring these approaches to the capabilities and constraints of each practice setting. This includes establishing eligibility criteria for outpatient management based on clinical stability, caregiver support, and logistical considerations such as proximity to care

Education is another critical domain. Pharmacists are deeply involved in training clinical staff across the care continuum, including nurses, advanced practice providers, physicians, and acute care teams. This education focuses on recognizing and grading toxicities, adhering to established protocols, and understanding the typical clinical course of BTCE-related AEs.

Taken together, these responsibilities position pharmacists as central to the successful implementation of BTCE programs. They bridge the gap between clinical evidence and real-world practice, ensuring that complex therapies can be delivered safely and consistently across diverse care environments. Their contributions span protocol development, systems design, clinical management, education, and strategic planning—making them indispensable to the multidisciplinary teams responsible for advancing BTCE care.

REFERENCE

Adams B, Peters B, Resnick Y. Strengthening the community pharmacist’s involvement in operational workflows for BsAb therapy. Presented at: 2026 COA Annual Meeting. April 28-29, 2026. Orlando, FL.