Bispecific Antibodies in Multiple Myeloma Are Moving From Clinical Trials to Community Practice

Two decades of advances in the management of multiple myeloma (MM) have significantly increased patients’ overall survival (OS). A recent presentation at the American Society of Hematology showed that approximately one-third of patients in one study lived at least 10 years after diagnosis,¹ and modeling of the now-standard quadruple therapy found that patients could live up to an additional 17 years.²

Not every patient with MM will have this experience, of course. Survival rates remain poor for those patients who progress after 3 lines of therapy.³ However, in recent years, multiple new therapies have received FDA approval, including chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies. As these therapies reach more patients, clinicians need data and real-world advice on how to integrate them into clinical practice, especially in the community setting.

To address this need, The American Journal of Managed Care^® hosted a Stakeholder Interchange on August 21, 2025, in New York, New York. During the session “Advancing Care for Multiple Myeloma: Strategies for Integrating Bispecific Antibodies in Clinical Practice,” moderator Nicholas Bouchard, PharmD, guided a discussion that addressed knowledge gaps between administering bispecific antibodies fully within the academic setting—where most clinical trials have occurred—and doing so as a partnership between a hospital and a community practice. Bouchard is the director of pharmacy services at Hematology-Oncology Associates of Central New York.

The session also examined what guidelines from the National Comprehensive Cancer Network (NCCN) say about the administration of bispecific antibodies for MM as well as strategies for community adoption, from how to build collaborations with academic partners to ways to overcome access barriers.

The discussion featured the following participants:

• Tarun Wasil, MD, a hematologist-oncologist with New York Cancer & Blood Specialists
• Genevieve Kumapley, PharmD, BCOP, clinical pharmacy manager, Holy Name Medical Center
• Marina Reed, PharmD, BCOP, clinical pharmacy coordinator, NewYork Presbyterian-Brooklyn Methodist Hospital
• Jaime Chin-Hon, PharmD, MS, BCOP, clinical pharmacist, NYU Long Island at Mineola
• Marina Barsoum, PharmD, BCOP, clinical pharmacy lead, NewYork-Presbyterian Brooklyn Methodist Hospital

Sequencing Therapy in Multiple Myeloma

Bouchard opened a discussion on sequencing therapies in MM, noting that CAR T-cell therapy and bispecific antibodies each offer advantages and downsides. CAR T is a 1-time, durable therapy. In MM, it works by collecting T cells and genetically modifying them to target the protein B-cell maturation agent (BCMA) found on myeloma cells.

However, manufacturing can take up to 6 weeks, and not all patients can wait that long. If patients have already received multiple lines of chemotherapy, their T cells may be exhausted. And CAR T-cell treatments are expensive, given the customized manufacturing process for each patient.⁴

As Bouchard explained, bispecific antibodies have been approved for different targets, as follows:

• Teclistamab (Tecvayli; Johnson & Johnson), elranatamab (Elrexfio; Pfizer), and linvoseltamab (Lynozyfic; Regeneron) target BCMA and CD3. BCMA is overexpressed in nearly all multiple myeloma cells. According to information Bouchard presented, the binding of ligands to BCMA enhances cell proliferation and survival.
• Talquetamab (Talvey; Johnson & Johnson) binds to GPRC5D, which is highly expressed in multiple myeloma cells, with little to no expression in other immune cells, and to CD3.⁵

“They are independent of each other, so you can express BCMA or GPRC5D, or you could express both of those particular proteins,” Bouchard said. “So, loss of BCMA expression does not affect GPRC5D expression.”

But as he shared, the big difference affecting sequencing is that the FDA allows CAR T-cell therapy to be used earlier in course of treatment. Ciltacabtagene autoleucel (Carvykti; Johnson & Johnson) can be used as early as the second line, whereas idecabtagene vicleucel (Abecma; Celgene) is approved as early as the third line. Bispecifics, Bouchard stated, were approved by the FDA for patients who have been treated with at least 4 prior lines of therapy, including an anti-CD38 therapy, a protease inhibitor, and an immunomodulatory drug. The most recent NCCN guidelines for multiple myeloma, published July 16, 2025, list all 4 approved bispecific therapies as preferred in this setting.⁶

This is where sequencing gets interesting. “Median overall survival [is] 11.6 months after reaching this triple-class refractory status,³ with more therapies available,”³ Bouchard said. “Data are needed on how to best sequence novel therapies and select the optimal regimen for patients.”

Step-Up Dosing: Community Practice or Referral to Academic Center?

Bouchard then addressed the core issue of bringing bispecifics for MM to community practice: What can clinicians expect compared with results in clinical trials? Can step-up dosing be handled from the start in an experienced community practice, or must this phase always be referred to an academic center?

Participants reported a variety of strategies. “We send them to our tertiary care centers for step-up dosing, and then in a month or so, patients come back to us,” Wasil said.

But managing relationships can be touchy, he said, especially in a hugely competitive region. Unlike lightly populated areas of the country—where hospitals might be thrilled to have far-flung community practices help them deliver bispecifics—doctors in Wasil’s practice are navigating a high-stakes environment.

Wasil explained that physicians in his practice have privileges across dozens of different hospitals, and for the use of outpatient bispecifics to thrive, physicians need to nurture these partnerships. “But it’s hard to come up with any one policy, because every hospital has their own different interests,” he said. “Being in New York, it’s a big problem because we have so many tertiary care centers for the group of patients, as well.”

Barsoum offered a different perspective: At her institution, the infusion center is across the street, and most patients just continue therapy there as outpatients. “We do accept referrals if other providers can’t provide for those patients inpatient,” she said.

Some of the panelists mentioned the Risk Evaluation and Mitigation Strategy (REMS) drug safety program, in which the FDA mandates that both institutions and providers be certified. Although there has been some easing of REMS requirements in CAR T-cell therapy, these remain for bispecifics in MM, Bouchard said.⁶

He then reviewed safety data, comparing major clinical trial results with real-world findings for 3 of the bispecific therapies, as follows:

Teclistamab. Data from the phase 2 MajesTEC-1 trial (NCT04557098)⁷ showed 72% of participants had cytokine release syndrome (CRS), with grade 3 or higher CRS in less than 1% of patients; 3% reported immune effector cell-associated neurotoxicity syndrome (ICANS), with 0% being grade 3 or higher. Infections were seen in 76.4% of patients; grade 3 or higher, 44.8%. In a 15-center real-world study—in which 89.0% of participants would not have been eligible for MajesTEC-1—54.0% had CRS, with 1.4% having grade 3 or higher; 11.0% had ICANS, with 2.2% having grade 3 or higher. Infections were seen in 42% of participants; 22% of infections were reported as “serious.”⁸

Elranatamab. Data from the phase 2 MagnetisMM-3 trial (NCT04649359)⁹ showed the following: CRS, 56.0%, with 0% grade 3 or higher; ICANS, 3.0%, with 0% grade 3 or higher; infections, 69.9%, with 46.3% grade 3 or higher. A 34-patient retrospective analysis showed that 32.0% of patients reported CRS, all grade 1 or 2; 14.7% had ICANS, with 2.9% grade 3 or higher. Infections were seen in 11 patients (32.4%); of these, 7 required hospitalization.¹⁰

Talquetamab. Bouchard presented data from 2 different dosing schedules in the phase 2 MonumenTAL-1 trial (NCT04634552).¹¹ The first cohort received 0.4 mg/kg once weekly, and the second received 0.8 mg/kg biweekly. CRS was seen in 79% of patients taking the first dose compared with 75% taking the second. In both cohorts, 11% of participants developed ICANS. Infections were seen in 61% of the first cohort and 71% of the second. A real-world study of 63 patients in 7 centers reported 63.0% developed CRS, with 1.6% grade 3 or higher; 13.0% had ICANS, 1.6% grade 3 or higher; and 37.0% had infections.¹²

In addition, Bouchard presented safety data for linvoseltamab, a new bispecific approved July 2, 2025.¹³ The phase 1/2 LINKER-MM1 trial (NCT03761108) has reported the following safety trial data: adverse events (AEs), grade 3 or higher, 73.5%; CRS, any grade, 46.0%; ICANS, any grade, 7.7%.¹³

What Do the NCCN Guidelines State?

The most recent version of the NCCN guidelines does not recommend one bispecific over another. The guidelines do state that, although patients can receive more than 1 BCMA-targeted therapy, “optimal sequencing of sequential BCMA-targeted therapies is not known; however, accumulated data suggest immediate follow on with [a] second BCMA-directed therapy after relapse may be associated with lower response rates.”⁶

The NCCN guidelines go on to address an issue that was a topic of extended discussion during the session: when and how to use prophylactic tocilizumab (Actemra; Genentech) before bispecific dosing to prevent CRS. The guidelines state that tocilizumab can be “considered prior to the first dose to reduce the risk of CRS.”⁶

Bouchard went over studies evaluating the use of prophylactic tocilizumab, notably the phase 2 OPTec trial (NCT05972135), which is using the therapy prior to the first step-up dose of teclistamab in an outpatient setting. Data published by Rifkin et al on 13 patients enrolled at 12 sites show that no patients have experienced CRS or ICANS, and none required hospitalization due to receiving teclistamab or tocilizumab.¹⁴

The discussion participants noted how much easier payer authorization for tocilizumab has become since its inclusion in the NCCN guidelines; previously, some experts had told AJMC that there was reluctance to order it for prophylactic use if payers refused to cover due to the cost for Medicare beneficiaries.¹⁵

Bouchard also discussed ongoing studies involving combinations with bispecifics—including a combination of combination of teclistamab and talquetamab that the NCCN has listed as “useful in certain circumstances.”⁶ Data presented on this combination show it is a potent weapon against myeloma, but it does have more serious AEs.¹⁶ However, Johnson & Johnson is among those developing a trispecific designed to address this issue by targeting BCMA, GPRC5D, and CD3 with less toxicity.

Managing Relationships and Patients

Bouchard talked about the work it took to convince a hospital system in the Syracuse, New York, area, where his practice is located, to form a partnership to deliver bispecifics. “Our patients typically go there when they’re too sick to be at home, obviously,” he said. “But it took a lot of education and convincing of the hospital administration [that] if we had an issue,will you be willing to take these patients?”

He added, “We had to educate their [intensive care unit] staff. We educated their [emergency department; ED] staff. They have a cancer wing, as well, where they treat [patients with] acute cancer. But it’s a bit of a lift for us, and that was probably one of our biggest barriers…. Luckily, we had a good relationship with them to start with, but it still did take some work to get them to agree to do it.”

Kumapley said there was initial reluctance to deliver bispecifics at Holy Name Medical Center in Teaneck, New Jersey, as well. But because it is a clinical teaching hospital, there was recognition that this was not something to avoid. She compared the learning process to what the staff went through when everyone had to learn about immunotherapy: It seemed scary at first, but now it’s well understood.

“We had a physician champion really engaging with a critical care specialist and pulmonologist and [neurologist]—that was a strategy—and really communicating that this is becoming the pathway, this is the future,” she said. “This was a huge opportunity.”

Kumapley added, “Obviously, pharmacy was a huge component of that, providing education, working with our nursing colleagues.” The pharmacy team took note of how apprehensive some colleagues were, especially about managing CRS. More education was offered to help staff understand the difference between grade 1 and anything higher than grade 1.

The panelists spoke in detail about treating patients at home: What is the optimal call schedule? Who makes the calls? How much dexamethasone do patients take home? And what criteria are used to bring patients in if they experience symptoms?

They also shared simple tips to keep patients safe should they have to go to the ED, such as carrying a wallet card or wearing a medical bracelet. Most of all, even if the oncology team has visited the ED, the patient may need to remind the emergency physician that they are not on old-fashioned chemotherapy, Bouchard said.

“You’re really educating the patient [that they are] not on chemotherapy. This is very different. Use those kinds of terms. It is very important to really drive that point home, because emergency medicine physicians won’t know the [extent] of this. Almost all patients have cell phones, so I usually take a picture [of the label] and store it in their phone,” he said.

See related article on a discussion of 3 case studies.

References

1. Fernandez RA, Barea AA, Romero MTC, et al. Unraveling long-term survival of multiple myeloma patients, the GEM2000 experience. Blood. 2024;144(suppl 1):1957. doi:10.1182/blood-2024-211383
2. Sonneveld P, Zweegman S, Facon T, et al. Modeling long-term progression-free survival in transplant-eligible and transplant-ineligible newly diagnosed multiple myeloma treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. Presented at: 6th European Myeloma Network Meeting; April 10-12, 2025; Athens, Greece. Abstract B04.
3. 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
4. The economics of CAR T-cell therapy. Association of Cancer Care Centers. 2024. Accessed October 6, 2025. https://www.accc-cancer.org/docs/projects/car-t-cell-therapies/the-economics-of-car-t-cell-therapy.pdf
5. Advancing care for multiple myeloma: strategies for integrating bispecific antibodies in clinical practice. AJMC. August 21, 2025. Accessed October 4, 2025.
6. NCCN. Clinical Practice Guidelines in Oncology. Multiple myeloma, version 2.2026. Accessed October 5, 2025. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
7. 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
8. Razzo BM, Midha S, Portuguese AJ, et al. Real-world experience with teclistamab for relapsed/ refractory multiple myeloma from the U.S. Myeloma Immunotherapy Consortium. Blood Cancer Discov. Published online July 9, 2025. doi:10.1158/2643-3230.BCD-24-0354
9. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9
10. Grajales-Cruz AF, Hansen DK, Castaneda O, et al. Safety and efficacy of standard of care (SOC) elranatamab in patients with relapsed/refractory multiple myeloma (RRMM), a single center experience. Blood. 2024;144 (suppl 1):7832. doi:10.1182/blood-2024-204276
11. 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
12. Shaikh H, Lochner J, Loeffler B, et al. Talquetamab in B cell maturation antigen (BCMA) exposed relapsed-refractory multiple myeloma patients. Blood. 2024;144(suppl 1):5170.4. doi:10.1182/blood-2024-211018
13. Klein HE. FDA approves linvoseltamab to treat R/R multiple myeloma. Am J Manag Care. 2025;31(suppl 9):SP558-SP559.
14. 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 2024 ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA.
15. Caffrey M, Joszt L. Operationalizing bispecifics in multiple myeloma. AJMC. November 27, 2024. Accessed October 6, 2025. https://www.ajmc.com/view/operationalizing-bispecifics-in-multiple-myeloma
16. Cohen YC, Magen H, Gatt M, et al; RedirecTT-1 Investigators and Study Group. Talquetamab plus teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;392(2):138-149. doi:10.1056/NEJMoa2406536