Lucy Bailey, CRNP

The final segment looks ahead to future directions in follicular lymphoma management while emphasizing the essential partnership between academic and community practices. Dr. Mehta describes how evolving therapies, particularly bispecific antibodies, are increasingly being adopted in community settings, supported by collaborative frameworks that allow patients to receive advanced treatments while minimizing travel burdens. The faculty highlight ongoing clinical studies suggesting that bispecific antibodies may soon move into frontline settings for both follicular and large B-cell lymphoma. Dr. Mehta predicts that over the next several years, a majority of community practices will gain the capacity to deliver bispecific therapy independently, mirroring trends already seen in solid tumor settings. The discussion transitions to CD19-directed approaches, including tafasitamab and loncastuximab, and how these therapies complement CD20-based strategies. The importance of checking CD19 expression at relapse is emphasized when considering sequencing and future CAR T eligibility. In concluding remarks, Dr. Mehta outlines key messages for clinicians: R2 is no longer the standard of care in relapsed follicular lymphoma; newly approved regimens have demonstrated superior efficacy; and therapy selection should be guided by practice resources, patient goals, and toxicity profiles. The program ends with a forward-looking perspective on how novel therapeutics and collaborative care models will continue to elevate patient outcomes in relapsed/refractory follicular lymphoma.

The experts next focus on clarifying the therapeutic goals for patients with transformed follicular lymphoma, particularly older adults. NP Bailey emphasizes that treatment goals must balance disease control, symptom reduction, hospitalization avoidance, and overall quality of life, while also recognizing that transformation introduces a potential opportunity for cure through aggressive modalities such as CAR T-cell therapy. Dr. Mehta and Bailey discuss how rapid disease progression may necessitate interim therapies to stabilize the patient until definitive treatment can be delivered. They revisit the diminishing role of autologous transplant in this population, noting that CAR T-cell therapy has largely supplanted transplant as the preferred curative-intent strategy. The segment also highlights the importance of individualized decision-making. Age alone should not exclude patients from cellular therapy, but comorbidities, functional reserve, and social support structures must be carefully assessed. The faculty stress the importance of realistic goal setting, clear communication, and aligning treatment intensity with patient priorities. This segment offers a nuanced discussion of how to approach transformed disease with both clinical rigor and patient-centered care principles.

This segment presents the program’s second case: a 72-year-old man with prior R-CHOP and R2 exposure who now demonstrates rapid progression, rising lactate dehydrogenase (LDH), B symptoms, and bulky lymphadenopathy, features highly suggestive of transformation to an aggressive lymphoma. The faculty walk through the clinical evaluation, emphasizing the importance of biopsy confirmation, especially when rising LDH and bulky disease raise suspicion for high-grade transformation. This segment highlights how transformed disease often behaves aggressively and requires a distinct treatment paradigm from indolent follicular lymphoma. NP Bailey outlines key considerations, including assessment of performance status, organ function, comorbidities such as diabetes and renal impairment, and the patient’s ability to tolerate intensive therapies. The discussion then shifts to potential treatment strategies, including CAR T-cell therapy, which may offer curative potential even for older adults. Dr. Mehta describes the roles of “holding” and “bridging” therapies in CAR T workflows, noting that rapid disease control may be necessary before leukapheresis or cell infusion. He comments on the limited data surrounding the addition of tafasitamab or epcoritamab after recent R2 exposure but emphasizes that clinical judgment and disease biology guide decision-making. This segment provides a comprehensive view of managing transformation, underscoring how clinicians must pivot quickly from indolent lymphoma strategies to aggressive lymphoma principles, while still considering the unique needs of older, comorbid patients.

This segment expands on the logistical framework needed to safely deliver bispecific antibodies in the outpatient setting. Dr. Mehta and NP Bailey outline how toxicity profiles, particularly CRS and ICANS, shape monitoring protocols and determine whether a community practice can administer bispecific therapy independently. Dr. Mehta emphasizes the advantage of having a 24/7 extended care clinic capable of managing grade 1–2 CRS with tocilizumab or corticosteroids, thereby preventing unnecessary emergency department visits or hospital admissions. He describes how proximity to such resources enables more widespread outpatient implementation of bispecific therapies. Bailey adds that patient education serves as the first line of safety, ensuring patients can recognize early symptoms, follow escalation instructions, and maintain adherence to therapy. She describes strategies for empowering patients, particularly older adults, to understand severe but rare risks while reducing unnecessary anxiety. The discussion underscores the strain on inpatient services nationwide and the growing push toward outpatient administration of bispecific therapies. As community practices build capacity and academic partnerships deepen, the segment predicts broader adoption of bispecifics outside major cancer centers. Clinicians gain insight into the infrastructure, communication pathways, and patient management strategies needed to deliver these therapies safely and efficiently.

Building on the prior case, this segment explores the practical distinctions between tafasitamab-R2 and epcoritamab-R2 in routine practice. Dr. Mehta notes that tafasitamab-based therapy is generally easier to administer within community oncology settings because it does not require the step-up dosing protocols or intensive monitoring associated with bispecific antibodies. In contrast, epcoritamab-R2, although highly effective, introduces complexities such as CRS risk, ICANS monitoring, and potential need for rapid escalation to emergency or extended care services. NP Bailey addresses patient education and adherence, emphasizing that epcoritamab-containing regimens require robust teaching around symptom recognition, infection prevention, and timely reporting of adverse effects. She underscores the importance of ensuring patients understand the seriousness of potential bispecific-related toxicities, even if uncommon, and have clear instructions for seeking care. The segment also highlights the operational realities of community practice, where many clinicians still rely on academic centers to initiate bispecific therapy before transitioning patients back to local care. Dr. Mehta notes the value of extended care clinics that can manage lower-grade CRS on an outpatient basis, reducing hospital admissions and relieving pressure on inpatient services. This segment equips clinicians with a pragmatic understanding of how to safely and effectively integrate novel antibody-based regimens into diverse practice environments.

Segment V introduces the program’s first clinical case: a patient who initially responded well to bendamustine-rituximab (BR) but now presents with symptomatic relapse, mild cytopenias, abdominal fullness, and B symptoms. This case illustrates a common and clinically challenging scenario, prompting the faculty to walk through their decision-making process. NP Bailey highlights that this patient is clearly beyond the window for watchful waiting and requires treatment intervention. She reviews therapeutic considerations following prior BR exposure, noting that re-treating with bendamustine is less appealing given newer, more effective options and the timing of relapse. The discussion centers on the choice between tafasitamab-R2 and epcoritamab-R2, two newly approved regimens demonstrating strong efficacy in relapsed follicular lymphoma. The faculty compare practical aspects of these therapies, including route of administration (IV vs subcutaneous), step-up dosing requirements, monitoring demands, and feasibility in community vs academic settings. Lenalidomide management again emerges as a key theme, particularly given the patient’s mild cytopenias. The faculty discuss strategies for initiating therapy at a lower dose and titrating as tolerated to maintain both efficacy and quality of life. This case provides a real-world demonstration of how novel bispecific- and CD19-based regimens fit into treatment sequencing and illustrates the importance of individualized therapy based on disease characteristics, patient comorbidities, and logistical considerations.

The experts focus on antibody-based therapies and the historical role of rituximab-lenalidomide (R2) in relapsed follicular lymphoma. Dr. Mehta explains how R2 served as a foundational second-line regimen before the introduction of CAR T-cell therapy and bispecific antibodies. Although still effective and widely used, its position in the treatment algorithm has shifted as newer options demonstrate superior efficacy and novel mechanisms of action. NP Bailey provides practical insights into using R2 in real-world practice. She discusses common toxicities, particularly fatigue and cytopenias, and describes how comorbidities such as cardiovascular disease and diabetes influence tolerability. The segment also emphasizes the importance of lenalidomide dose adjustments, especially for older adults or those with baseline cytopenias. Bailey notes that clinicians have substantial flexibility in dosing without compromising effectiveness, allowing therapy to be individualized to patient tolerance. The faculty highlight how patient perception of “non-chemotherapy” regimens like R2 can influence acceptance, while also acknowledging that oral therapies require strict adherence and frequent monitoring. As newer combinations such as tafasitamab-R2 and epcoritamab-R2 emerge, the segment frames R2 as a useful but increasingly transitional therapy. This discussion provides clinicians with a realistic view of how R2 fits within today’s broader therapeutic landscape.

Segment III explores how clinicians approach second-line therapy in follicular lymphoma, particularly as new options challenge traditional standards. Dr. Mehta reviews how CD20-directed therapies have historically anchored relapse treatment but notes the shift toward more diverse targets, including CD3 (via bispecific antibodies) and CD19 (via tafasitamab and other emerging agents). This expansion raises important clinical questions around target sequencing, resistance, and whether using a target early may “burn” it for future lines of therapy. The discussion highlights the role of bispecific antibodies, CAR T-cell therapy, and CD19-based agents, along with practical considerations such as infusion requirements, monitoring demands, and access to treatment centers with specialized capabilities. Dr. Mehta explains how academic-community partnerships influence real-world treatment pathways, especially for therapies with more complex toxicity profiles like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). NP Bailey contributes perspective on patient logistics, including distance to treatment centers, social support needs, and how the complexity of treatment may shape patient decision-making. She emphasizes the importance of aligning therapy selection with patient lifestyle and functional status, a theme that recurs throughout the program. This segment underscores the increasingly individualized nature of second-line therapy, where clinicians must integrate disease biology, treatment history, patient comorbidities, and practical feasibility. As the faculty outline, modern management requires balancing efficacy with safety, accessibility, and long-term planning, ensuring that patients receive not only effective but sustainable care.

Together, they emphasize that relapse evaluation must go beyond radiographic progression alone. Some patients may demonstrate disease progression on imaging but remain clinically stable enough for continued surveillance. Others develop symptomatic relapse, requiring prompt intervention. The faculty describe the importance of understanding disease tempo, symptom burden, and patient goals when determining whether and when to initiate second-line therapy as components of personalized care.

This segment outlines how clinicians today approach initial management, recognizing that improved survival and expanding treatment choices have dramatically changed the patient journey. As Mehta and Bailey note, frontline success does not eliminate the likelihood of relapse, making it essential to anticipate how early decisions may influence subsequent therapeutic sequencing.