Overcoming Pain Points to Advance Bispecifics in the Community for Patients With Myeloma

There’s great potential to administer bispecific antibody therapy at the community level for patients with multiple myeloma—if the hurdles can be overcome.

Regulations must be followed, providers and patients need education, and some cannot receive initial bispecific treatment in the outpatient setting due to the lack of a caregiver, according to experts from the Seattle, Washington, area who gathered on November 20 for the final 2025 Stakeholder Interchange presented by The American Journal of Managed Care^®.

Yet these are also hopeful times for the use of bispecifics in myeloma care. At the time of the discussion, both panelists and the moderator, Sophia Humphreys, PharmD, MHA, BCBBS, vice president, Health System Strategy and Innovation at MJH Life Sciences, were excited about the abstracts to be presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida. Several studies promised to move bispecifics into earlier lines of care.¹ And the Seattle group discussed the promise of biosimilar versions of a key prophylactic therapy that could prevent cytokine release syndrome (CRS), a common adverse reaction to bispecifics.

Panelists taking part in the discussion were:

• Osler Andres, PharmD, infusion specialist at Pacific Medical Center’s Canyon Park Infusion Pharmacy;
• Danai Dima, MD, myeloma specialist and assistant professor, Clinical Research Division, Fred Hutch Cancer Center; assistant professor, Division of Hematology and Oncology, University of Washington School of Medicine;
• Grace Baek, PharmD, BCOP, clinical oncology pharmacist, University of Washington Medicine/Fred Hutch Cancer Center;
• Richa Thakur, MD, physician, Fred Hutch Cancer Center; assistant professor, Division of Hematology and Oncology, University of Washington (UW) School of Medicine;
• J.T. Lew, PharmD, BCPT, managed care pharmacist, Multicare Health System; and
• Vikramsinh M. Dabhi, MD, PhD, hematologist/oncologist, Pacific Medical Centers and Swedish Hospital System.

Unmet Needs and Current Treatment Landscape

As Humphreys noted, a retrospective analysis by COTA’s health database suggested a medium overall survival rate is a little less than a year, just 11.6 months, after patients reach triple-class refractory status.² Thus, there is an urgent need for new treatments, and a void that bispecific antibodies could fill. Yet barriers limit adoption, despite the known challenges with another novel treatment, chimeric antigen receptor (CAR) T-cell therapy.

“You guys all know the pain,” Humphrey said of CAR T-cell therapy. “The manufacturer sometimes takes up to 6 weeks. And it’s very patient-specific.” The complexity of CAR T-cell therapy manufacturing and its associated costs³ have created an opening for bispecific antibodies, which may offer a more accessible option.

Current guidelines recommend bispecific antibodies after 4 prior therapies, typically including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory drug, Humphreys said,⁴ noting, however, that the lack of clear sequencing recommendations between bispecific antibodies and CAR T-cell therapy for patients who have exhausted 4 lines of treatment creates decision-making challenges for clinicians.

In the Seattle area, Dima said, community practices “don’t really do step-up dosing. I think when we get a patient from the community that’s referred to us, usually the patients are referred to us for CAR T vs a bispecific.” This highlights a critical gap—many community practices lack the infrastructure or confidence to initiate bispecific therapy, leading to a centralization of care that may not suit patients’ needs.

Step-Up Dosing: Academic vs Community Implementation

The administration of bispecific antibodies requires careful step-up dosing to mitigate CRS and immune effector cell–associated neurotoxicity syndrome (ICANS). As Humphreys said, with “all of the bispecifics, we still have to enroll all of these patients into REMS programs,” referring to Risk Evaluation and Mitigation Strategies. “So, our pharmacy and our physician both have to go through that. And the step-up dosing sometimes is used to mitigate the initial risk for toxicities.”

The discussion revealed differences in how academic centers and community practices approach step-up dosing. Dima noted that most community referrals involve the academic center performing the step-up dosing before returning patients to their local oncologists for maintenance therapy. “I know that there are some places that do the step-ups,” she said. “I just feel like these places don’t really refer the patients to us. They just do everything themselves.”

Baek emphasized the importance of standardized handoff processes. “How do we hand off patients after step-up dosing? You know, the uncomplicated, no CRS or ICANS patients, that’s pretty simple, cut and dry. There’s a lot of evidence.” However, she said the complicated cases that require ongoing coordination remain challenging, particularly when patients receive care across multiple health systems.

Thakur added perspective from her previous experience in New York, where “at some centers that have extensive multicenter care, a lot of the step-up dosing is always done in the main site, but then the peripheral sites will do the BiTEs [bispecific T-cell engagers] to whomever they want.” This model recognizes that not all satellite facilities have the capacity for overnight admission and intensive toxicity monitoring, she explained.

Geographic considerations also play a role in these decisions, Thakur said. “I have another patient, for example, in Alaska that I’m considering [for] bispecifics. And the oncologist is very comfortable doing it in June and July. But it’s November, and give another 2 weeks, and the patient lives maybe 30 minutes from the hospital, God forbid there’s a snowfall.”

REMS Requirements and Regulatory Challenges

REMS requirements can present significant barriers to community adoption of bispecific antibodies, panelists said. As Andres explained, “I guess the most obvious one is when you follow REMS, it’s very highly regulated, and it’s following the package insert. So oftentimes when the package insert mandates monitoring in the inpatient setting, you’re kind of stuck doing that.”

Lew said just the training to enforce the REMS requirements was daunting. This increases the challenge of finding qualified oncology technicians for non–hospital-based infusion centers.

Dima said it’s not that difficult for physicians to be REMS certified, but for pharmacists, it’s a steep climb. “I have to be really honest. I just follow the link that Grace [Baek] sends me, and I just reply to some nonsense questions. I think for the pharmacy department to go through the REMS is much more complicated.” Community pharmacy departments typically have fewer resources than their academic counterparts, making REMS compliance a greater burden, she said.

Andres provided additional context about regulatory oversight variations: Pacific Medical is state-certified as a licensed pharmacy, but not all community oncology centers are. For practices operating under physician licenses without state board oversight, REMS requirements can be especially intimidating.

There are practical issues, Thakur said. When a REMS program is established for teclistamab (Tecvayli; Johnson & Johnson), “for the REMS program for teclistamab and linvoseltamab [Lynozyfic; Regeneron] or talquetamab [Talvey; Johnson & Johnson], even just getting that second authorization and setup is a huge barrier.”

Baek described how Fred Hutch streamlined their REMS processes through iteration and centralization: “When teclistamab first came out and we were getting used to the REMS process, I think there was definitely a growing process in terms of establishing a centralized authorized representative.” They evolved from a decentralized system where “clinical pharmacists at the point of verification of teclistamab” documented codes to a more efficient centralized model.

Prophylactic Tocilizumab: A Game Changer

As with other AJMC^® Stakeholder Interchanges, the moderator presented data comparing the percentages of patients with CRS in clinical trials and the much smaller shares seen in real-world studies.⁵

Today, more patients receive prophylactic tocilizumab, which the Seattle group said has had a powerful impact on outpatient bispecific administration. “It’s been actually great,” Dima said. “We’ve been using [tocilizumab] for the majority of our patients that we do give bispecifics in the outpatient, but also in the inpatient side.”

Her preference is to give tocilizumab to every patient receiving a B-cell maturation antigen–directed bispecific, recommending a dose given an hour before the first step-up dose.

Dima acknowledged pragmatic considerations when dealing with payers, however. “Sometimes you just have to balance how long the insurance authorization will take vs how urgently the patient needs treatment,” she said. Tocilizumab can prevent hospitalizations or a trip to the emergency department (ED), but while CRS can occur, “it’s pretty rare for the patients to get CRS, but the vast majority of events are grade 1 or 2.”

Baek described how the inclusion of tocilizumab in the National Comprehensive Cancer Network (NCCN) guidelines has eased payer coverage. “When we just had teclistamab come out and we attempted a similar initiative, we were pretty firmly shut down by our billing team just because we didn’t have that NCCN wording at that point. But now that prophylactic tocilizumab is in the NCCN guidelines, we’ve definitely had [an] easier time getting authorization.”

Lew addressed the insurance perspective, expressing optimism about the coming availability of biosimilar versions of tocilizumab.⁶ “Honestly, what I’m really just hopeful and optimistic for is that, especially now that we have tocilizumab biosimilars available, is that payers are going to be able to be more generous with the coverage.” He noted that coverage issues sometimes relate not to the molecule itself but to “which formulation of it, essentially, the biosimilar vs innovator product,” with some plans implementing biosimilar-first policies.

The panel discussed how tocilizumab biosimilars, despite lacking the specific CRS indication due to “skinny labels,” can be utilized through therapeutic interchange protocols.

Infrastructure and Staffing Requirements

The panel identified critical infrastructure requirements for safe outpatient bispecific administration. Dabhi emphasized 2 key factors: “One is your staffing and training, and the second is the location,” he said. His institution, for example, is not near a hospital, “so that requires a different level of confidence vs our downtown location because it affords you an immediate hospital visit.”

He drew parallels to earlier concerns about outpatient rituximab administration. “When we opened a clinic in Canyon Park, I used to get pushback about giving rituximab. And from a couple of the nurses, they would be like, ‘Well, Vik, if this happens, what are you going to do, and how are we going to manage it?’ Now, I never get pushback about doing that. They’re like, ‘Oh, we’ll be able to manage it.’ And that was just time and comfort level.”

Dima said there can be variability within single systems. “Even at Fred Hutch, we have some satellite places where they have the Fred Hutch name, and sometimes patients think we can do everything there, but we can only do bispecifics and step-up dosing at Fred Hutch, Maine.” Some satellite locations cannot administer maintenance bispecifics, she said.

Baek outlined essential components for safe outpatient administration, beginning with patient education and point-of-contact protocols. “At Fred Hutch and UW, we admit all of our patients who experience CRS. But even before we get to that step, we had to discuss, ‘Who’s going to be the first point of contact? How is a patient going to know to get a hold of us?’” Patients receive education from clinical pharmacists and nurses, have prescriptions for emergency dexamethasone, and learn how to maintain thermometers at home, she said.

The challenge of after-hours coverage emerged as particularly critical, Baek explained. “During business hours, it should be pretty easy. We have a team on site,” she said. “But weekends, holidays, after hours—who is going to be assessing the patient and determining, is this fever due to infection? Is this fever due to CRS? What are the next steps?”

Daily assessments are essential, Dima said. “If we do outpatient bispecifics, they have to be assessed every single day...in our institution, we do assessment by APP [advanced practice provider] or MD on the day of step-up dosing. But then the rest of the days, the patient still comes in, and they’re getting assessed by nursing.” Adequate staffing is essential, because “the physicians out there, they see 20, 30 patients per day. It’s not possible that they can assess the same patient while going through step-up dosing every single day.”

The panel also highlighted the importance of shared electronic medical records (EMRs). Andres said, “We’re spoiled in Providence [Health System]…we’re in PacMed because we are part of a greater system that has the same EMR…if you’re in a community setting that does not share the EMR with the hospital, that can be a significant barrier.”

Dima raised concerns about ED preparedness. A patient’s community oncologist may say the practice can handle step-up dosing, but then the question comes, “Can you just take the patient after? They’re always like, ‘What if something happens? Like, where do I send the patient? The hospital we send our patients to, we don’t share the same EMR. The ED physicians, they’re not trained.’”

Thakur added that even with shared EMRs, the ED and the hospitalist face barriers, as “access to the notes isn’t necessarily just enough to solve a discomfort.”

Patient Selection, Caregiver Support, and Empowerment

Selecting the right patients for outpatient treatment remains crucial for successful outpatient bispecific therapy, the group said. Dabhi noted that for “patients with comorbidities, it’s not going to happen in the community setting. It’s going to be at a hospital or adjacent hospital setting.” The oldest patients will have challenges, too.

Caregiver support emerged as a nonnegotiable requirement. “We need to remember that these patients should have a caregiver when they’re going through step-up,” Dima said. “These first 10 days, there should be somebody with them even if they’re doing outpatient,” because caregivers provide essential advocacy. If a patient has no caregiver, inpatient administration becomes necessary.

But at least this is an option. “It’s so much easier to do that for bispecifics compared to CAR T because we know CAR T,” Dima said. “They won’t give CAR T if there’s not a dedicated caregiver.”

Dabhi said patients must be trained in care management in this time of limited resources. He described providing select patients with emergency medications. “For patients who I can trust…I say, here are some antibiotics. Now, if you get into a pinch and you start having fevers and you can’t get to one of us, you just start this antibiotic.” He applied the same logic to dexamethasone for CRS management.

“By the time you get to the [ED] and go through the triage and wait…it can be hours,” he said. “But if you take some ownership, it kind of helps actually manage a lot of things quite well.”

“There just aren’t enough staff. There aren’t enough nurses. There aren’t enough doctors,” Dabhi said. “So, if you don’t take this approach of arming patients, then what you’re going to do is just end up excluding patients from getting the treatments that you want because you don’t have the capacity to treat them.”

Andres highlighted the importance of education across all levels. “If we don’t have that experience, the best thing we can do is educate. So, educate at all levels—nursing, pharmacy, even the patient level.” He called for clear memoranda of understanding that define “who has a responsibility, who is accountable for making sure all these things fall into place when [an] emergency happens.”

Quality of Life and Supportive Care

An often-overlooked aspect of bispecific therapy emerged in discussions about dose de-escalation and quality of life. Dima advocated for early de-escalation. “Instead of every week, you can go to every other week and every month pretty quickly, actually. I tend to do that pretty early, after 3 or 4 cycles, because that actually makes the quality of life of the patients better, like less risk for infection and long-term complications.”

She explained the rationale: “I always tell patients in bispecific, listen, if you get a month, a month, and a half of bispecific and you don’t respond, it’s really highly unlikely that you’re going to respond at some point in the future. Whereas if you really have a good response after the first month or two, then this response will most likely be maintained in the future, even if we decrease the frequency of bispecific.”

Beyond acute toxicity management, the panel emphasized comprehensive long-term care. “I think we should also be aware of the long-term care of these patients,” Dima said. “IVIG [intravenous immunoglobulin] is really important. Infectious prophylaxis is really important.”

Humphreys presented survey data showing variability in prophylactic approaches across 15 physicians at 9 cancer centers, covering herpes simplex and zoster, pneumonia, pseudomonas, yeast, mold, and viral coverage. This variability underscores the need for standardized supportive care protocols.

Dabhi predicted that bispecific adoption would rise as physicians gain experience, and community adoption would follow patterns seen with other therapies. “As time goes along, we’ll get better at this. And we’ll probably not follow the package insert exactly because we already do that for PD-L1s.... I think you’re going to see the same thing transpire as time goes along because of the response rates, and the opportunity affords you the option of playing with your dosing.”

As Lew concluded, the discussion provides “such a good teaching moment” about “how can the care delivery systems teach people on the insurance plan side how to ask the right questions of their community partners that can provide care?”

References

1. Caffrey M. Bispecifics in new combos, new uses, and earlier lines of treatment in myeloma. AJMC. December 15, 2025. Accessed December 22, 2025. https://www.ajmc.com/view/bispecifics-in-new-combos-new-uses-and-earlier-lines-of-treatment-in-myeloma
2. Wang PF, Yee CW, Gorsh B, et al. Treatment patterns and overall survival of patients with double-class and triple-class refractory multiple myeloma: a US electronic health record database study. Leuk Lymphoma. 2023;64(2):398-406. doi:10.1080/10428194.2022.2140284
3. Keesari PR, Samuels D, Vegivinti CTR, et al. Navigating the economic burden of multiple myeloma: insights into cost-effectiveness of CAR-T and bispecific antibody therapies. Curr Hematol Malig Rep. 2025;20(1):3. doi:10.1007/s11899-024-00748-5
4. NCCN Clinical Practice Guidelines in Oncology—Multiple Myeloma. Version 4.26. Published November 26, 2025. Accessed December 23, 2025. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
5. Caffrey M. Bispecific antibodies in multiple myeloma are moving from clinical trials to community practice. Am J Manag Care. 2025;31(spec 11):SP825-SP827.
6. Serani S. FDA expands approval for tocilizumab biosimilar to treat CRS. Targeted Oncology. August 7, 2025. Accessed December 22, 2025. https://www.targetedonc.com/view/fda-expands-approval-for-tocilizumab-biosimilar-to-treat-crs