Expanding Access to Bispecifics in Myeloma While Navigating Reimbursement Nuances

Across the country, bringing bispecific antibodies to more patients with multiple myeloma will require collaboration between academic centers and community practices to learn how to integrate these therapies into the outpatient setting—and then determine which patients are the best candidates for this setting.

But all markets have their own dynamics, and the regulatory and reimbursement nuances of the region that encompasses Maryland, Virginia, and Washington, DC, can affect where patients receive treatment as health systems and practices take on both the clinical challenges and financial risks associated with bispecific antibodies in myeloma.

On November 18, 2025, a panel of oncology experts convened in Washington, DC, to address the challenges of expanding access in the session “Advancing Care for Multiple Myeloma: Strategies for Integrating Bispecific Antibodies in Clinical Practice,” a Stakeholder Interchange presented by The American Journal of Managed Care^®. Moderated by Jody Agena, PharmD, MBA, director of pharmacy operations at Virginia Cancer Specialists, the panel featured a diverse group of providers from across the region:

• Kevin Brigle, PhD, ANP, a nurse practitioner specializing in myeloma at Virginia Commonwealth University’s Massey Cancer Center;
• Andre Harvin, PharmD, MS, BCPS, chief pharmacy officer, University of Maryland Medical System;
• Minhee Kang, PharmD, BCOP, BCPS, clinical manager, oncology and research pharmacy, MedStar Georgetown University Hospital;
• Kieron Dunleavy, MD, director of hematologic malignancies, MedStar Georgetown; and
• Matthew Reilley, MD, medical oncologist, University of Virginia Medical Center (UVA).

Fear of the Unknown Can Be Greater Than Reality

Agena noted that survival rates in patients with triple-class refractory multiple myeloma remain poor, creating an urgent need for effective therapeutic options.¹ According to current guidelines from the National Comprehensive Cancer Network, bispecific antibodies are recommended after at least 4 prior therapies, although this is evolving, he said. Most patients have already received anti-CD38 therapy, an immunomodulatory drug, and a proteasome inhibitor. Enrollment in the Risk Evaluation and Mitigation Strategy (REMS) program, which is required for all bispecific therapies, “may be an obstacle in your smaller community settings,” Agena said.

The complexity extends beyond regulatory requirements. Panelists discussed their approaches to step-up dosing in acute care settings, along with premedications and careful monitoring protocols. Recreating these protocols outside the academic center and moving them into the community can create operational challenges, they said, both for the community practice and for hospital partners that support efforts to move these therapies to the outpatient setting.

The panelists discussed the wariness their teams felt when they first took bispecific antibodies into the outpatient setting, which eased as they learned what to expect, especially with cytokine release syndrome (CRS).

Harvin had previously worked to bring bispecific antibodies to rural settings through Cone Health in North Carolina, and both he and Kang described how the fear of CRS and immune effector cell–associated neurotoxicity syndrome (ICANS) can be greater than the reality.

In North Carolina, “A lot of us came together—pharmacy, medical, nursing—to have several committee discussions on what that would look like,” he said. “Before I left, we [had] been up and running doing bispecifics in the community for [patients with multiple myeloma and lymphoma] for about 5 months.”

“When you actually see it, the incidence of CRS and ICANS was significantly less than what we assumed,” he continued. “So much of it was about education and having consistent processes.”

Dunleavy said insights from Georgetown’s experience implementing outpatient bispecific therapy for patients with lymphoma, which began approximately 2 years ago, offered lessons for starting outpatient myeloma treatments. “The very first patient I treated, which I don’t usually do, I gave him my cell phone number, and I was just really worried that he was going to [experience] CRS and not respond to his temperature going up,” Dunleavy recalled.

Within weeks, the team’s comfort level increased, and Dunleavy credited pharmaceutical company support as instrumental, particularly for nursing education in the infusion center.

Patients receiving bispecifics for myeloma “require more monitoring,” he said, and are “sicker than the [patients with lymphoma].” Patients with multiple myeloma frequently present with significant comorbidities, and “a lot of patients have renal issues because of myeloma,” making outpatient management more complex.

At Georgetown, Kang said, there was similar early caution, driven by package inserts that recommended hospitalization or required inpatient step-up dosing. The first 3 bispecific antibodies approved in myeloma all had more than 70% CRS in clinical trials, she noted.

However, actual experience proved reassuring. “We didn’t really see grade 3 CRS,” Kang reported, giving the team confidence to plan outpatient implementation. This required extensive preparation, including development of monitoring protocols, prespecified protocols in the electronic health record—known as power plans—and comprehensive educational initiatives.

The scope of education efforts went far beyond the oncology team. “Nursing education is another big portion of this outpatient bispecific therapy movement initiative,” Kang said. Her team had to reach outpatient nurses unfamiliar with CRS and ICANS, emergency department (ED) staff who might see patients with complications, and inpatient pharmacists who would need to recognize and manage toxicities.

Georgetown developed detailed implementation checklists and criteria for determining which patients were appropriate for outpatient vs inpatient administration. “We have to set up the criteria, which patients are more eligible for outpatient, and which ones [we] have to admit on the inpatient side,” Kang explained, acknowledging the need for case-by-case evaluation.

Infrastructure and Staffing Requirements

Harvin explained at length how Maryland’s capitated reimbursement model affects the University of Maryland Medical System, which can only predict a certain number of inpatient treatments, with additional cases resulting in financial losses. This created strong incentives to move patients to the outpatient setting quickly.

However, reality is something else. “About 50% of all of our patients that end up being treated with either [chimeric antigen receptor T-cell therapies] or bispecifics come from outside of a University of Maryland facility,” Harvin noted, creating enormous strain on the system. Despite aggressive efforts, only about 30% of bispecific treatments occurred in the outpatient setting; he said there is a goal of reaching 50% by June 2026.

Brigle said Virginia Commonwealth University remained entirely inpatient for bispecific administration but was developing innovative solutions. He described plans to utilize a clinical decision unit rather than the ED, allowing direct admission to a specialized unit where tocilizumab could be administered if needed. The institution was also considering prophylactic tocilizumab, though reimbursement remained a barrier.

Financial and Reimbursement Considerations

Financial toxicity and reimbursement challenges emerged as critical themes throughout the discussion. Agena described Virginia Cancer Specialists’ cautious approach: “A denial at the back end would kill us. And so, we were very sensitive to that, and our physicians were as well.”

The practice began performing teclistamab (Tecvayli; Johnson & Johnson) and talquetamab (Talvey; Johnson & Johnson) ramp-ups on a case-by-case basis, carefully evaluating patient selection and caregiver support. Initially, concerns about off-label dosing or settings created anxiety, but experience demonstrated that careful documentation and appropriate patient selection generally resulted in coverage.

“It still takes a lot of buy-in from the others, not just the heme team,” he said, because nurses and physicians who end up being on call are also affected. And in the end, “for a Medicare patient, you’re looking at your reimbursement, and it’s not that great.”

Community practices must look at delivering bispecifics as part of a long-term strategy, he said.

A discussion on tocilizumab raised similar tensions. Multiple centers reported routine denials for prophylactic tocilizumab despite literature supporting its use. As Brigle put it, “If we sucked up the tocilizumab cost, but you saved 5 days of admission, which one’s cheaper?”

Calculating the total cost of care has proved elusive. Harvin said, “We can’t actually get to it, because it has to do with, are you going to change your staffing? Can you staff less nurses, staff less pharmacists, if you’re reducing inpatient utilization?”

Maryland’s capitated model has created unique dynamics. “If you go any volumes over what you predicted for the year, it’s just all a financial loss,” Harvin said. This made expensive inpatient therapies particularly problematic, yet the state limited how quickly patients could be shifted to outpatient settings to prevent cost-shifting.

Payer type significantly affected authorization processes. Kang noted that commercial insurance was “easier, because they do have a very clear thing,” with transparent approval or denial decisions. Meanwhile, government payers without prior authorization requirements could come back years later with retrospective medical necessity reviews.

Innovative Models and Technology Solutions

Several panelists described innovative approaches to managing outpatient bispecific therapy. UVA developed an extended clinic model for tarlatamab (Imdelltra; Amgen) in lung cancer, keeping patients in the infusion center until 9 or 10 pm to bridge the monitoring gap. “It’s cheaper to keep them and just pay a physician and some nurses extra time to monitor them” than risking admission for CRS, Reilley explained.

Harvin described an impressive system at Geisinger Health in Pennsylvania that leveraged Epic’s eSymptom module for remote patient monitoring. Patients received automated prompts on their phones to report symptoms hour by hour initially, with the care team receiving real-time updates through a command center. “It was alerting the team in the background through, like, a scoring system” when symptoms developed or progressed unexpectedly, Harvin explained.

This technology-enabled approach provided physicians peace of mind while minimizing unnecessary contact. The system both facilitated asynchronous communication through MyChart and triggered phone calls when escalation was needed, with nurse navigators and pharmacy team members monitoring patients and escalating to physicians only when necessary.

Multidisciplinary Team Requirements

Success in implementing outpatient bispecific therapy required robust multidisciplinary support. Dunleavy emphasized the importance of having “somebody that the patient can call 24 hours” with buy-in from covering teams. Georgetown’s fellow and attending structure provided this safety net, but Dunleavy acknowledged that practices without such systems faced greater challenges.

Navigator teams played crucial roles in multiple centers. Harvin described how patient concerns about treatment costs immediately triggered navigator involvement to review benefits, help with enrollment in assistance programs, and identify financial support resources. “Their whole goal is to shepherd the patient from beginning to end and ensure that if they do run into something that could be a financial toxicity, that they’re raising the red flag,” Harvin explained.

Georgetown employed revenue integrity pharmacists specifically dedicated to prior authorization processes and peer-to-peer preparation. Kang said this specialized role had been implemented about a year ago and had significantly improved authorization success rates and streamlined workflows.

Education and Training Needs

Educational requirements extended across multiple stakeholder groups. Outpatient nursing staff needed training in recognizing and managing CRS and ICANS—complications they rarely encountered compared with their inpatient colleagues. Kang noted that nurses wanted “visible, the guideline, in this nursing unit, so they can see it right there” rather than relying solely on electronic resources.

ED education presented particular challenges; as Kang explained, ED staff and hospitalists must all be prepared for potential admissions. Pharmaceutical company support is valuable, but the ultimate responsibility rests with individual practices and health systems.

Brigle suggested that national emergency medicine organizations represented important educational targets, arguing that “there’s a great place to educate at their national meetings” rather than placing the entire burden on oncology teams.

Barriers to Community Adoption

REMS certification emerged as a significant barrier to community implementation. Brigle highlighted the contrast between lymphoma and myeloma bispecifics. The certification process requires substantial investment and ongoing maintenance, presenting particular challenges for smaller community practices, he said, adding, “No one in our community is REMS certified for any of the myeloma bispecifics,” despite willingness to administer lymphoma bispecifics after step-up dosing.

Geographic considerations complicated outpatient implementation. While formal distance mandates varied by institution, practical considerations required patients to live within a reasonable proximity to an academic center or have access to lodging. Kang mentioned offering hotel accommodations for patients from distant areas, while noting that Georgetown didn’t have strict distance requirements like those mandated for transplant patients.

Patient selection criteria included general fitness, comorbidity burden, and caregiver support availability. Dunleavy noted that Georgetown had successfully treated many patients in an outpatient setting but acknowledged, “Of course, there would be” patients inappropriate for outpatient treatment due to comorbidities. However, he observed that even patients with comorbidities often tolerated bispecifics well in the outpatient setting.

Different reimbursement models created varying incentives and barriers. Maryland’s capitated system made inpatient administration particularly problematic financially but restricted how quickly patients could transition to outpatient care. “You get a 15% cap on doing that,” Harvin explained. “So, if you treated X number inpatient last year, 15% of that can move to outpatient the next year.”

Value-based arrangements created different pressures. Harvin described North Carolina’s Cone Health as operating under arrangements where “about 60% of our patient volumes were on a value-based arrangement,” making them “really penalized for that inpatient stay.”

Fee-for-service Medicare patients often experienced the smoothest authorization processes. Reilley appreciated “the Medicare patients that are not Medicare Advantage, because in my experience, they are able, we’re able to get people started really quick. Sometimes same day, because no prior [authorization] is required.” However, Medicare Advantage plans proved more challenging, with Reilley candidly noting, “That’s where I get burned.”

Strategies for Successful Implementation

Panelists repeatedly emphasized the importance of academic-community partnerships. Harvin’s North Carolina experience demonstrated how Duke University, the University of North Carolina, Wake Forest University, East Carolina University Health, and Cone Health collaborated to ensure consistent care processes across settings. This collaboration proved particularly valuable for rural populations who might otherwise lack access to bispecific therapies.

The partnership model extended to patient referrals and management. Georgetown, Maryland, and UVA all reported referring patients back to community practices after step-up dosing, though this required trust and communication. Agena confirmed that Virginia Cancer Specialists’ patients returned after Georgetown-managed ramp-ups, dispelling initial fears about losing patients to academic centers.

Successful implementation required phased approaches with substantial up-front investment. Dunleavy advised, “When you start doing this, you’ve really got to kind of have all of the resources up front, and even over-resource for the beginning of the project, basically, and then as people get more used to it, it’s easier to de-escalate resources.”

This principle includes staffing, where dedicated teams proved essential initially, and monitoring, where more intensive protocols could be relaxed as practices gain experience. The lymphoma bispecific experience at Georgetown demonstrated this trajectory, with initial anxiety and heavy resource use giving way to routine administration within months.

Physician Leadership and Champion Development

Multiple panelists emphasized the need for dedicated physician champions. Dunleavy stated, “To get it started, you have to have a dedicated team. Of course, the attending who is treating the patient is in charge of the team, but you have to have that team in place; otherwise, it’s very tricky to initiate this.”

Harvin reinforced this point from the community perspective: “You’ve got to make sure you’ve got the right physician champion, and they’re going to be supported. Like, it’s not just all new work that they’re going to be doing on the weekends and nights.”

Agena noted the expanding need for champions beyond hematology, particularly as tarlatamab gained traction in solid tumors: “Now you need another champion on the solid-tumor side, as far as being, like, the gung ho physician leader.”

Future Directions and Emerging Therapies

More changes are in store, with trispecific antibodies promising the possibility of reduced adverse effects compared with bispecific combinations.² “One of our studies has a trispecific in one of the arms as well. So that’s, I think, those are going to be better than these, than the swap in between the 2 of them,” Brigle said. “The [adverse] effects are so much easier [to manage].”

The proliferation of similar agents raised formulary management questions. With multiple BCMA-targeting CD3 bispecifics available or in development, pharmacy and therapeutics committees faced difficult decisions about how many functionally similar drugs to maintain on formulary. As Brigle asked, “How do you justify having the exact same drug, basically, on a group?”

Emerging data from solid tumor applications suggested different toxicity profiles that would require adaptation. Reilley noted seeing “amazing responses in people who’ve been refractory to everything else, but like a lot more CRS, a lot more issues with that. So, I think there’s going to be a lot of, like, tailoring to the specific tumor type and therapy in the future.”

Kang emphasized the importance of collaboration and emerging real-world data to determine appropriate timing for community referral, while Harvin expressed hope that within 5 to 7 years, “most oncology care is done in the community,” extending critical therapy access through continued collaboration.

“It’s going to require, I think, looking at maybe the success of lymphoma bispecifics, and having, like, a team effort, if we want to operationalize, having these in community settings,” Dunleavy said.

Agena believes the investments and partnerships will be worth it. “This is definitely going to outpatient, and it’s probably going to be 100% outpatient at some point in a few years,” he said.

References

1. 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
2. A study of JNJ-79635322 in participants with relapsed or refractory multiple myeloma or previously treated amyloid light-chain (AL) amyloidosis. ClinicalTrials.gov. Updated December 5, 2025. Accessed December 21, 2025. https://clinicaltrials.gov/study/NCT05652335