Forging Partnerships to Bring Bispecifics to the Outpatient Setting in Myeloma

Advances in multiple myeloma care include the use of bispecific T-cell engagers, which can offer patients durable benefits without the turnaround times needed for chimeric antigen receptor (CAR) T-cell therapy.

Talquetamab (Talvey; Johnson & Johnson), which binds to GPRC5D and CD3, and teclistamab (Tecvayli; Johnson & Johnson), elranatamab (Elrexfio; Pfizer, Inc), and linvoseltamab (Lynozyfic; Regeneron), which bind to BCMA and CD3, can be viable choices for patients who have exhausted other options and have comorbidities that make them ineligible for CAR T.

The desire to deliver bispecifics outside academic centers, thus bringing treatment closer to patients, was the topic of a dinner conversation in the Atlanta, Georgia, area on November 4, 2025. Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of pharmacy at Emory Healthcare and Winship Cancer Institute, moderated the discussion with the following participants, who came from both academic and community centers:

• Ajay K. Nooka, MD, MPH, FACP, hematologist, Emory Winship Cancer Institute
• Nisha Joseph, MD, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine
• Justin D. Austin, PharmD, MBA, director of pharmacy, Atlanta Cancer Care/Northside Hospital Cancer Institute
• Remco Witteveen, PharmD, director, Oncology Pharmacy Services, Northside Hospital
• Sara Ann Scott, PharmD, BCOP, clinical pharmacy specialist in multiple myeloma, Emory Healthcare
• Han Le, PharmD, CPh, MHA, pharmacy manager, Grady Health System

The conversation started with a fundamental question: What has been their experience with initiating step-up dosing in community vs academic settings?

“We have 5 hospitals, so we're not doing step-up dosing in all 5 hospitals," Witteveen said of Northside’s strategy. "We started at the Atlanta hospital because we have our [bone marrow transplant (BMT)] group there. So, they were very knowledgeable, obviously, with CAR T and knowing how to handle those patients." The system has since expanded to a second hospital with strong medical oncology coverage and daily rounding capabilities.

The primary barrier? "Medical oncologists just being uncomfortable," Witteveen said.

Austin's experience at Atlanta Cancer Care highlighted the importance of physician champions. Early on, "one of our physicians was really asking and looking into this and really curious,” he said. This enthusiasm created momentum, but the practice still opted for a hybrid approach: performing dose escalations inpatient with the BMT group, then transitioning patients back to community care. This model allowed the outpatient team to prepare while minimizing risk during the highest-toxicity window.

Joseph, offering the academic perspective, said Emory typically receives referrals for the relapse/refractory setting and performs the cycle 1 ramp-up before considering transition back to community providers. There are ongoing efforts to make the process “more accessible and more predictable” for community partners, she said. Anxiety around cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remains palpable, with concerns of, “What do I do if this happens at 2 in the morning? How do I do this outpatient?”

Prophylactic Tocilizumab Proves to Be a Game Changer

There was extended discussion on the use of prophylactic tocilizumab, or toci, which has emerged as a cornerstone strategy for reducing CRS and enabling outpatient administration. The Emory team has taken the lead with this approach, producing data supporting its effectiveness.

Scott and Joseph explained how Emory initially administered tocilizumab before the second step-up dose, but discovered that giving it before the first dose worked even better. "We really try to reduce that CRS rate down quite low by giving toci," Joseph said. She, Scott, and Nooka were among the authors of a 2023 abstract at the American Society of Hematology that showed only 30% of patients who received prophylactic tocilizumab prior to teclistamab experienced CRS,¹ compared with 72% in the pivotal trial that led to FDA approval of the drug.²

The economic justification for using tocilizumab this way proved crucial to achieve buy-in, Haumschild explained. “When you do the total cost of care analysis,” he said, the cost of having increased inpatient costs against DRG, or charge to a diagnosis-related group, to manage CRS would significantly offset the prophylactic treatment. With biosimilar versions of tocilizumab now available at approximately $1000 per dose, the investment easily pays for itself by avoiding even a single-day hospitalization, which at Emory costs around $2500. For outpatient administration, the economics are even more favorable.

Nooka emphasized the broader principle. "I believe these could be given very, very safely in the community when you combine both [dexamethasone] and [tocilizumab] in the first week or first 2 weeks, and we don't need to hesitate to give these drugs." He cited teclistamab data that show 0% CRS rates with combined dexamethasone and tocilizumab prophylaxis.³

Today, Emory administers tocilizumab before the first step-up dose and repeats it only if patients experience breakthrough CRS. With a half-life of approximately 11 days, a single prophylactic dose covers the highest-risk period, Joseph said, including the first 2 doses of agents such as linvoseltamab.

Comparing Safety Data in Clinical Trials vs the Real World

The discussion highlighted important discrepancies between clinical trial data and real-world experiences with bispecific safety profiles. Haumschild presented data from MajesTEC-1 (NCT04557098), the pivotal trial for teclistamab, which showed CRS in 72% of patients, with grade 3 or higher in less than 1% and ICANS around 3%.² However, a retrospective real-world study involving 509 patients receiving teclistamab across 15 centers showed CRS in 54%, with grade 3 or higher at 1.4%, but ICANS jumped to 11%.⁴

Similar patterns emerged with talquetamab: the pivotal clinical trial, MonumenTAL-1 (NCT04634552), showed CRS at 79% while real-world data from Moffitt Cancer Center demonstrated CRS at 59.3% with ICANS at 14.8%.^5,6 These differences sparked discussion about patient selection, prophylactic strategies, and evolving management protocols.

Joseph, Scott, and Austin provided important context about ICANS with bispecifics vs CAR T-cell therapy. Austin said ICANS has more nuances and can be challenging to monitor; he called for more education in evaluating this condition, as “it’s still kind of murky.”

"CAR T-cell therapy is a very different ball of wax with ICANS and the late neurotoxicities, but with bispecifics, first of all, the rates are quite low,” Joseph said. She and Scott emphasized that with bispecifics, ICANS typically occurs during the initial ramp-up period following CRS, not as an isolated late event.

“ICANS is very uncommon, but when you see CRS, it's at that initial ramp-up, maybe cycle 1,” Joseph said. “Once you get through that ramp-up, you shouldn't be seeing that.”

The practical implication: Once patients complete the step-up dosing phase, the primary concerns shift from acute cytokine-related toxicities to more manageable chronic issues such as cytopenias and infections—complications familiar to all oncologists.

Education Builds Confidence Across the Care Continuum

A recurring theme throughout the evening was the critical need for comprehensive education targeting multiple stakeholders: physicians, advanced practice providers, nursing staff, emergency department personnel, and patients with their caregivers.

Witteveen described Northside's approach to emergency department education: "We've done some education in the [emergency departments (EDs)] at our hospitals so they're aware—so obviously the patients having wallet cards and things like that, knowing to present them, but then also educating the [EDs] about what to look for when a patient walks in with the wallet card."

For patients and caregivers, Emory has developed a pocket dex program where patients receive education about fever monitoring and preemptive medication to use at home. If a fever develops, patients take Tylenol, Benadryl, and dexamethasone before presenting to the Intermediate Care Center (ICC)—Emory's 24-hour hematology-oncology-specific emergency facility. This protocol provides patients with a sense of control while ensuring appropriate triage.

Joseph emphasized the importance of straightforward, realistic education: "When I educate our patients, I tell them no getting pregnant, no donating blood…You have a malignancy, and you're being treated with anticancer therapy."

Financial Considerations for Institutions and Patients

Panelists addressed the complex financial landscape surrounding bispecific therapies, from institutional cost-benefit analyses to patient out-of-pocket expenses and insurance authorization challenges.

Haumschild explained Emory's approach to prophylactic tocilizumab. "Economically, it's an outpatient observation encounter. So, if you're giving toci, if you're giving IVIG [intravenous immunoglobulin], there's a different reimbursement structure as opposed to taking the hit against a DRG." Payers have recognized the value in this model because it reduces the total cost of care.

The cost justification required data. Haumschild described being asked by finance to "spot check the difference between claimants that have CRS management vs DRG reimbursement and those that have prophylactic toci." The team's published data helped solidify approval for inpatient use, which then served as a pilot for expanded outpatient implementation.

For 340B institutions such as Emory and Grady, significant price differences exist between inpatient and outpatient drug costs, adding another dimension to administration-setting decisions. Haumschild noted, "Inpatient [tocilizumab], we're not getting reimbursed separately for that, but if that's reducing length of stay for a patient and one day longer at Emory's $2500 for a net cost and you're paying less than that for one dose of [tocilizumab], the more money you can save, you're a captain on that DRG reimbursement."

Nooka raised questions about patient out-of-pocket costs, noting that the Inflation Reduction Act capped out-of-pocket prescription drug costs at $2000 for Medicare patients starting in 2025. However, Haumschild clarified that this cap applies only to the outpatient pharmacy benefit (Medicare Part D). Since bispecifics are infusibles for the medical benefit, patients still face 20% coinsurance for this portion.

The good news: Most patients either meet their deductibles early in treatment or access manufacturer assistance programs to offset costs. Additionally, numerous myeloma-specific grants exist. Said Scott, "There are so many myeloma grants available, and they can be used for infusion as well, which I think a lot of people think they just have to use it for their [lenalidomide], but it can be used for infusion coverage."

Le highlighted Grady's unique resource: a partnership with the Georgia Cancer State Aid Program, which reimburses up to $65,000 for cancer treatment as a payer of last resort. Transportation assistance, including vouchers and valet parking subsidies, addresses another significant barrier for vulnerable populations.

Authorization and Access

Prior authorization emerged as a persistent frustration across settings. "Many payers are very nearsighted,” Austin said. “So, while that conversation completely makes sense and logically they should engage, they're very nearsighted about what is happening today."

The transition of patients between academic and community settings can trigger authorization complications. Haumschild explained, "Usually it'll be a 6-month authorization. If it's lower cost, they'll give us a 12-month authorization." However, when tax IDs differ between institutions, payers may question whether authorization applies, potentially causing treatment delays.

Looking ahead, formulary restrictions loom. Haumschild referenced payers such as Centene, the largest manager of Medicaid coverage, potentially narrowing coverage to 2 BCMA bispecific options. Scott said she has warned manufacturers, “you're probably going to have to start lobbying the payers because that's where decisions are going to come from, unfortunately.”

While much attention is focused on CRS and ICANS, the participants emphasized that chronic infection risk represents the most significant ongoing challenge with bispecific therapy. Joseph stated emphatically: "I would take out ‘consider for IVIG’ and just say when you're giving bispecific antibodies, you should be giving monthly IVIG, period."

The rationale is compelling. B-cell depletion from bispecifics creates profound immunodeficiency. Monthly IVIG supplementation, combined with Pneumocystis jirovecii pneumonia prophylaxis, has dramatically reduced infection-related complications and deaths compared with early phase 1 studies. Joseph noted that improved infection rates in real-world studies likely reflect the routine use of these prophylactic measures, which academic centers such as Emory and Moffitt Cancer Center have standardized.

Infrastructure Models and Patient Scheduling

Emory's Intermediate Care Center emerged as a potential model for treating patients who are receiving bispecific therapy for multiple myeloma, though participants acknowledged that not every institution can replicate this approach. The ICC functions as a 24-hour hematology-oncology-specific emergency department where patients can present for evaluation and treatment of bispecific-related complications.

The economic and clinical advantages are substantial. As an outpatient observation encounter, it avoids the 72-hour rule, where bispecific administration followed by admission would roll drug costs into the DRG. Patients avoid exposure to typical emergency department infections while receiving immediate access to providers with bispecific expertise.

What can institutions do when they lack this infrastructure? Options include designating specific emergency departments with focused education, which Northside has done; coordinating with academic center ICCs to refer community patients who have complications; creating formal protocols for emergency bispecific management; and selectively admitting higher-risk patients for step-up dosing.

The group discussed issues around scheduling and patient selection. For institutions without 24/7 oncology coverage, timing bispecific administration early in the week emerged as a key safety strategy. This ensures that if delayed CRS occurs (median onset is 24 to 48 hours for most bispecifics), medical oncology support remains available.

Emory's approach during its early ICC implementation illustrates this principle. Joseph said, "Everyone started on a Monday, and they only got dosed on weekdays, which is still our standard. We only do step-up on weekdays, but because of that 48-hour window, we wouldn't dose them after Thursday, knowing that the ICC was available on Saturday."

Patient selection criteria for outpatient step-up dosing include low disease burden, minimal comorbidities, reliable caregiver support, reasonable proximity to the treatment center, and the patient being known to the treatment team. Scott offered a practical rule of thumb. "Think of it as like a clinical trial patient, like someone who's kind of together."

Building Partnerships and Looking Ahead

Participants called for stronger partnerships between academic and community providers—one built on mutual respect, clear communication, and shared patient care goals. Joseph said she partners with Austin all the time, for example.

From the community perspective, Witteveen noted, “It means a lot to the provider back home” when academic colleagues demonstrate this collaborative spirit. Austin emphasized the importance of process formalization. “We created a process map…[to identify] who the owners are of these various steps and what do they need and when do they need it in the process.”

The academic team's commitment to sharing resources proved particularly meaningful. Scott’s offer to share protocols, order sets, and CRS/ICANS management smart sets drew enthusiastic response. "We want to develop that. We're publishing some of this to publish it and to get academic credit, but also to get it out there that this is how we're doing it," she explained.

Memoranda of understanding, clear communication pathways, and realistic time frames for authorization and onboarding all support successful transitions. Austin noted that when academic centers communicate transition plans with adequate lead time, "it gives them like a month's heads-up to start getting prepared, to start getting [Risk Evaluation and Mitigation Strategies] set up, to add it to the formulary, to figure out [if we] can order this to be able to get it wholesale."

Scott placed bispecifics within the broader evolution of cancer therapy: "We have antibody drug conjugates, we're going to trispecifics, we're going to be using CAR T-cell therapy earlier, we're going to be combining CAR T with bispecifics." Rather than viewing this complexity as overwhelming, she framed it as an opportunity for academic centers to pioneer protocols and share learning.

Joseph highlighted bispecifics' potential. "There's really not a population that wouldn't benefit from these drugs. And for an older, frail patient population, these drugs are as highly effective as monotherapy. They're subcutaneous, and they are monthly, and that's a pretty good deal for an 80-year-old patient."

Nooka delivered perhaps the most emphatic call to action: "The bispecific should not be given in an academic setting; they should be given in a community. And these are the drugs that everybody should be familiar with in the next 5 years."

He cited 160 ongoing trials with bispecifics across all oncologic indications. Even with a conservative 5% approval rate, these drugs will only proliferate. “These are not something that you want to wait for,” he said.

His advice to hesitant providers: "Eat the frog. You have no choice."

References

1. Marin E, Scott S, Maples K, et al. Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab administration. Blood. 2023;142 (suppl 1):2008-2009. doi:10.1182/blood-2023-189878
2. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478
3. Rifkin R, Schade H, Simmons G, et al. Optec: a phase 2 study to evaluate outpatient step-up administration of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM): updated results. Blood. 2024;144 (suppl 1):4753. doi:10.1182/blood-2024-207295
4. Razzo BM, Midha S, Portuguese AJ, et al. Real-world experience with teclistamab for relapsed/refractory multiple myeloma from the US Myeloma Immunotherapy Consortium. Blood Cancer Discov. Published online July 9, 2025. doi:10.1158/2643-3230.BCD-24-0354
5. Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(suppl 16):8036. doi:10.1200/JCO.2023.41.16_suppl.8036
6. Grajales-Cruz AF, Graeter A, Hansen DK, et al. Single center real world experience of talquetamab in patients with relapsed and refractory multiple myeloma. Presented at: 66thAmerican Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA. Abstract 3784. https://ash.confex.com/ash/2024/webprogram/Paper204232.html