Bridging the Gap: Implementing Bispecific Antibodies for Multiple Myeloma Across Care Setting

The landscape of relapsed/refractory multiple myeloma treatment has transformed dramatically with the introduction of bispecific antibody therapies. However, the transition from clinical trials to real-world implementation—particularly in community oncology settings—presents unique challenges. A September 30 discussion in Los Angeles, California, brought together oncology leaders from academic medical centers and community practices.

The group shared insights on safely expanding access to these promising therapies while managing the complexities of cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infection prophylaxis, and care coordination. Moderated by Sophia Humphreys, PharmD, MHA, then with Providence Health, the discussion featured the following participants:

• Geoffrey Shouse, DO, PhD, hematologist/oncologist at City of Hope
• Natasha Banerjee, MD, medical oncologist, Cedars-Sinai, Tarzana
• Melody Chang, MBA, RPh, BCOP, vice president of pharmacy operations, American Oncology Network
• Swati Sikaria, MD, oncologist/hematologist, Torrance Memorial Physician Network
• Ali Reza Rejali, PharmD, outpatient oncology pharmacy manager for Cedars-Sinai, Los Angeles
• Laura Quintal, PharmD, BCOP, clinical pharmacy specialist, UCSF Medical Center

Understanding the Unmet Need for Patients With Relapsed/Refractory Disease

Despite many advances in multiple myeloma treatment, the urgent need for solutions in the relapsed/refractory setting remains. Humphreys cited a recent study that found patients with triple-class refractory multiple myeloma survived less than a year.¹

“With more therapy available now, and with more data coming to us, we really want to know what’s the best regimen for them,” she said. Thus, it is important to expand access to therapies such as chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies—but implementation challenges abound.

“Some doctors are starting CAR T [in the] second line right now, and what they are seeing is that [prior authorization] takes a long time, manufacturing takes a long time, and there’s really a lack of financial assistance for these types of treatments,” Humphreys explained.

Both CAR T-cell therapy and bispecific antibodies target similar antigens, either B-cell maturation antigen or GPRC5D, a protein in the G protein-coupled receptor family.

Participants discussed how bispecific antibodies offer potential advantages in terms of manufacturing time and logistics.

The discussion touched on a controversial practice: using bispecific antibodies as bridging therapy while waiting for CAR T. Humphreys noted that “bridging is a dirty word” in some circles. When asked about this approach, Rejali acknowledged his institution uses it for this purpose with lymphoma patients.

Academic Center Experiences: Building Infrastructure for Safety

Academic medical centers have established protocols for bispecific administration, leveraging their experience with CAR T-cell therapy. However, even these well-resourced institutions face challenges.

Cedars-Sinai’s approach. Rejali described the current strategy. “We do see referrals, and being an academic center, we do offer all of the bispecifics at this time,” he said. Cedars-Sinai is working to bring bispecifics to the outpatient setting, but that has been a challenge due to monitoring requirements. Participants discussed the fact that the FDA has eliminated the Risk Evaluation and Mitigation Strategy (REMS) program for CAR T but requirements remain for bispecifics.

Travel times in Los Angeles also present a concern. “We’re always worried about sending the patients home,” Rejali explained, highlighting the need for “a proven, trusted remote monitoring system that can integrate with” electronic health records (EHRs).

UCSF’s integrated model. Quintal described a more established infrastructure built on years of clinical trial experience, both with CAR T and bispecifics. “We build into our EHR, which is Epic, all the REMS pieces,” she explained. “They try to remove that as a barrier, or get that addressed right away as a barrier. We also have a lot of people who deal with the financial aspect to make sure it’s covered.”

UCSF’s approach emphasizes comprehensive staff training across all care settings. “All our nurses are trained. And I think that’s a really important piece,” Quintal stressed. “Your staff need to be trained, and the patients [must be] trained to describe their symptoms and tell people.”

In addition, UCSF has standardized algorithms built into their order sets. “We build those things in, because CRS is always going to happen at a very strange time,” Quintal noted. “[It’s] not going to be at 5 pm or 3 pm. But those people who may not see it all the time need to be prepared.”

Patients are taught to advocate for themselves—a strategy that proves invaluable when they land in the emergency department (ED). As Quintal explained, if patients are “taught to advocate for themselves, that’s part of what helps our infrastructure succeed too, because they can tell the providers in the ED, I got this drug a week or two ago, and then that’s something they can look out for.”

City of Hope’s hotel model. Shouse described his institution’s model as cheating.

“We have a hotel on campus that we just built 2 years ago. It holds more patients than our inpatient beds, and we just built a 9-story outpatient center. So, our administration is invested heavily in the outpatient side of things because it’s financially a lot more prudent than inpatient.”

City of Hope’s model leverages this proximity advantage. “Most of our patients stay at the hotel and then come back and forth to our day hospital every day,” Shouse explained. The institution had already been performing outpatient CAR T for 2 years, so “we had all of the framework in place from that to just implement that for bispecific antibodies.”

The system includes specialized infrastructure: Patients have a dedicated phone number to call if they develop fevers or CRS, leading to immediate evaluation in a closed urgent care center that is open 24 hours but reserved exclusively for their patients. “We always have a backup person available who’s covering cell therapy patients, whether it’s CAR T or bispecific antibodies, and they’re available 24 hours a day for the week that they’re covering,” Shouse added.

City of Hope has even pushed boundaries further, beginning to perform selected allogeneic transplants in the outpatient setting. “We got some cowboys in our [allogeneic] transplant program for sure,” Shouse said, noting, “We don’t do any biomonitoring. They’re just in such close proximity, and we have the steps outlined so carefully, that we haven’t had any issues.”

AON’s Systematic Rollout Reaches Deep Into the Community

Academic institutions may start with an edge in infrastructure, but community practices have reach—and that’s proving essential as they show that with the right planning and education, they can bring bispecifics where the patients are.

Chang, representing American Oncology Network (AON), described an impressive systematic implementation across a large, geographically diverse network. “We’re operating in 22 states,” she explained. “We have practices throughout the United States. So, each clinic, each practice, might have a different setting.”

AON formally launched its program in April after an extensive education program. By the time of the September gathering, Chang said practices had given 1400 doses of bispecific therapy across the system.

The patient safety bracelet. Chang’s development of a patient identification bracelet with integrated educational resources was a huge hit with the group. “For every patient getting the bispecific, we give them this wristband [with] a barcode on it. And when you scan the barcode, it will bring you to all the side effects,” including CRS and ICANS management strategies and protocols.

The bracelet addresses a critical gap: When patients present to unfamiliar emergency staff, they can quickly access treatment protocols. “The ED doctor can just scan it, and they know how to deal with [the situation], what drugs to give,” Chang explained.

AON’s program includes careful risk stratification. Change said, “Is the patient reliable? What about the patient’s caregivers? Does the patient have a caregiver 24 hours?” Other key considerations are “the distance, the patient’s location, and how long [it takes] to get to the hospital or come to the clinic just in case something happens.”

The organization developed comprehensive standard operating procedures and checklists. When a physician puts in an order to start a patient on a bispecific, “it will trigger an alert to the pharmacy on our dashboard,” Chang said. In turn, this triggers verification of multiple readiness factors, including REMS certification.

Patients receive home monitoring kits and structured follow-up. “We also send patient home with a monitoring kit for free,” she said. “The triage nurse will call as a follow-up after the step-up dose for 24 to 48 hours. And the patients are supposed to come back the next day to see the doctors again and get the hydration.”

The results have been encouraging, she said. “Right now, I’ll say probably 20 to 30 patients are already on ongoing outpatient bispecific [treatment],” spanning nearly every state where AON operates.

The Role of Prophylactic Tocilizumab

The use of prophylactic tocilizumab generated diverse opinions. Humphreys noted, “Some would say, they’re going to need [tocilizumab] anyway, just give them 1 dose [of] prophylaxis, and I can sleep easy.... Some said, you know what? Only one-third of the patients would have CRS, and I’d rather wait until I need it.”

Data presented from the OPTec study showed zero CRS cases in 11 patients who received tocilizumab before first dose of treatment.² The University of Miami’s larger experience with 72 patients showed 14% CRS rates with prophylaxis. City of Hope’s Shouse indicated his institution uses prophylaxis routinely for patients with multiple myeloma, though not for those with lymphoma.

However, Quintal raised important practical concerns about cost. “[Tocilizumab] is not cheap,” she noted, explaining that as a health system expense in the inpatient setting, “that’s expensive...that’s something that your inpatient is going to take on as a cost.” She suggested that preventing severe CRS requiring intensive care might ultimately prove more cost-effective than prophylaxis but acknowledged the calculation remains complex.

From Fear to Confidence

Multiple participants emphasized that familiarity breeds competence in managing these toxicities. Shouse captured this evolution: “It’s such a clinically unique and characteristic process, once you’ve experienced it a couple times. If you haven’t, it’s terrifying. But if you have, then it’s just like, OK, I know what’s going to happen next.”

Chang emphasized the importance of systematic education. “What we need to invest in is to really just equip ourselves with full knowledge, skills, and [to] humble ourselves,” she said. “At the beginning, I borrowed everybody’s CAR T therapy [standard operating procedure] to put it together as our bispecific SOP.”

Sikaria was optimistic about community adoption. “I’m not really convinced that these patients really need to be in the hospital for the first 24 to 48 hours for that step-up dosing. So, my preference strongly would be to actually initiate this in the outpatient setting rather than the step-up inpatient.” Her community hospital already manages CRS for CAR T patients who live locally, so “we’re already managing CRS on the inpatient side. It’s not something new.”

Prior Authorization Challenges

Participants discussed various strategies for streamlining the prior authorization process, from leveraging EHR integration to more aggressive advocacy. Quintal said artificial intelligence (AI) may soon help. “In certain EHRs,” she said, “they build in now [so that] when you’re ordering the drug through their beacon system, it can send the prior authorization into a queue [and] can get that going, and then we’re implementing...AI models so that they can fill out that prior authorization quickly.”

Shouse shared his more confrontational approach when facing denials: “I have them blocking things because, for example, like in large cell lymphoma and [National Comprehensive Cancer Network] guidelines, the third-line setting for [diffuse large B-cell lymphoma] says, and anything in Table 2. And I’m getting something from Table 2, and they say, well, it’s not approved for the third line and beyond.” His solution? “I also encouraged my patient to seek legal counsel for the delay of care from their insurance company. And I say, please include that in the rebuttal, and it gets approved.”

Financial Toxicity

The discussion increasingly turned to what Chang termed “financial toxicity”—the devastating impact of treatment costs on patients. “This financial toxicity is no less than the actual toxicity you get from the treatment. Sometimes it could be even severe,” she said.

Humphreys shared a striking example: A nurse identified that a patient’s co-pay on Christmas Eve would be $24,000. This led to implementation of new protocols requiring insurance verification before treatment to ensure patients understand their financial responsibility. As Humphreys said, “20% of a half a million is a lot.”

The group expressed concern about proposed tariffs and drug pricing policies. The impact on a drug’s price “is going to be huge for the tariff [at]100%,” Chang observed, although she noted that pharmaceutical companies have many ways to respond.

Rejali raised a sobering reality for small practices: “Just because something is authorized does not mean that the physician actually will get that drug covered. I know a personal friend of mine who is an oncologist. He would purchase [pembrolizumab], and insurance would authorize it and give him a flat payment of $200 for a dose.” This led to his stark conclusion: “We can talk about all this all we want, but if a physician is going to be losing thousands of dollars, they’re not going to be picking up these bispecifics and giving them in the community.”

Referral Challenges and Transitions

Natasha Banerjee, MD, a medical oncologist with Cedars-Sinai in Tarzana, California, described the typical pattern: “Mainly the community sites refer to the main Cedars, and we do inpatient monitoring. We do not do it out in the community.” This is the reality, she said. “A community hospital out where we are would have no idea what to do with [certain] symptoms, and they would not recognize them at all.”

The challenges extend beyond initial treatment. “If our patients need to get admitted to the hospital, they might go to any one of 6 community hospitals in the area—one of them we can see our patients at, the others we do not have privileges at—so we really have no control over what happens if they go to a different hospital,” Banerjee explained. “We might even not get called by the hospital if they get admitted over there.”

Sikaria said community hospitals may lack essential medications. “It doesn’t help if the hospital they’re at doesn’t have tocilizumab. Because not all hospitals carry it,” she noted.

For academic centers, Shouse emphasized the importance of trust-building with referring physicians. “Make sure that the physicians know they’re going to get their patients back after the step-up dosing, and then really follow through and make sure they do,” he said. “That’s the way you get patients to come.”

City of Hope developed a formalized handoff note “for when we transition patients out of the cell therapy clinic back to their primary hematologist...it includes what toxicity they experienced, what we recommend as far as prophylaxis and for how long, what to do in certain situations, and what to expect from long-term toxicities,” Shouse said.

Telehealth and Remote Monitoring

The discussion concluded with consideration of emerging technologies that could further expand safe access to bispecific therapies.

Humphreys posed the question: “During COVID, we all developed telehealth. We even have a digital [intensive care unit]. Our nurses are trained; our physicians are trained. Can that be used in bispecific monitoring? Even in the beginning?”

Participants were generally enthusiastic. “Absolutely,” Sikaria responded, with Shouse agreeing. “I know there are some centers that do that for CAR T too. So instead of having a patient seen every day, they’ll be seen by a nurse a couple of days in a row by telehealth. And if anything needs to be escalated, then [the patient] comes for evaluation.”

Chang mentioned emerging AI applications, such as having patients do cognitive evaluations to screen for ICANS via AI. However, challenges remain with continuous remote monitoring devices. Chang identified 2 barriers: “One is the data integration. All the data monitoring still has to be entered through the manual effort.... The second challenge is, who is going to be responsible for getting [patients] notified?”

Shouse acknowledged additional complexities: “You get false alarms, you get all these things, and you have to have a way to get in touch with the patient to get the direction on what to do. You see the abnormal labs and things, or the abnormal vitals. It can be pretty complex.”

References

1. Tsang C, O’Reilly J, Carpenter L, et al. Comparison of outcomes with elranatamab and real world treatments in the UK for triple class exposed relapsed and refractory multiple myeloma. BMC Cancer. 2025;25(1):1219. doi:10.1186/s12885-025-14624-9
2. 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. Presented at: ASH 2024; December 7-10, 2024; San Diego, CA. Abstract 4753.