A new second-line standard of care is pulling patients with multiple myeloma into bispecific therapy earlier,oncologists and pharmacists from the Philadelphia region said during a stakeholder interchange on integrating bispecific antibody therapy into community and outpatient practice for patients with relapsed/refractory (R/R) disease.
With teclistamab (Tecvayli; Johnson & Johnson) plus daratumumab (Darzalex; Johnson & Johnson) now approved after a single prior line of therapy,1,2 panelists at the session held on July 21, 2026, said the shift is already reordering how and when community practices refer patients to academic centers for chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies.
The discussion, moderated by Sandra P. Susanibar-Adaniya, MD, MS, assistant professor of medicine (hematology-oncology) at the Hospital of the University of Pennsylvania in Philadelphia, included Adam D. Cohen, MD, director of myeloma immunotherapy and professor of medicine (hematology-oncology) at Penn Medicine; Moshe Chasky, MD, FACP, of Alliance Cancer Specialists; Shivani Kapur, MD, assistant professor of clinical medicine (hematology-oncology) at Penn Medicine; Andy Hui, PharmD, BCPS, a clinical pharmacy specialist at Hackensack Meridian Health (previously of Penn Medicine); Nissa Tasnim, PharmD, BCPS, an oncology clinical pharmacist at Jefferson Einstein Philadelphia Hospital; and Gloria Espinosa, PharmD, MAT, BCOP, an advanced clinical pharmacy specialist in malignant hematology at Thomas Jefferson University Hospitals in Philadelphia.
The conversation unfolded against a fast-changing treatment landscape. This year brought approval of ciltacabtagene autoleucel, or cilta-cel (Carvykti; Johnson & Johnson), as second-line CAR T-cell therapy3 and idecabtagene vicleucel, or ide-cel (Abecma; Bristol Myers-Squibb), as third-line therapy.4 But bispecific antibodies had required at least 4 prior lines, including anti-CD38 therapy, a proteasome inhibitor, or an immunomodulatory drug. That was before results from MajesTEC-3, presented at the American Society of Hematology Annual Meeting and Exposition in Orlando, Florida, in December 2025,1 moved teclistamab plus daratumumab into second-line use without requiring prior CD38 exposure.
Susanibar-Adaniya said the change already applies to patients who experience progression after standard triplets such as bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone followed by lenalidomide maintenance and noted that the National Comprehensive Cancer Network has deliberately avoided prescribing strict sequencing between CAR T-cell therapy and bispecifics “because we don’t know yet, right? We don’t know exactly with certainty which therapy needs to be first and which needs to be second.”
An Earlier Second-Line Standard Reshapes Referral Patterns
Panelists agreed that the shift toward earlier bispecific use is changing how and when community practices should engage academic partners. Chasky argued the relationship should start well before a patient needs treatment.
“I think the earlier the community gets the patient in, [the better]; I would say even from the beginning,” he said. “I think that should be fostered from the academic centers. That should be the message to the community: We’re going to work together from the beginning, even if it’s just a touchpoint, and see the patient every 6 months at the beginning so that they’re ready to go.”
Key Takeaways
Outpatient step-up dosing varies widely by site, driven less by comfort with the toxicity profile than by staffing, space, and after-hours coverage.
Staffing, not CRS biology, is the true bottleneck. Several panelists pointed to an overextended nurse practitioner or a small trained on-call pool as the true limit on program volume.
Payers have not caught up. Panelists described inconsistent coverage of prophylactic tocilizumab and intravenous immunoglobulin and warned that inpatient step-up dosing is not sustainable for community practices from a reimbursement standpoint.
He recalled a colleague’s dictum that most myeloma “can be handled in the community alone” only up to a point, after which academic input becomes essential—particularly for determining whether the patient is a candidate for transplant.
Kapur said the emerging data have made the choice between older regimens and bispecifics more straightforward for many patients. “I think it’s pretty clear from, at least, the MajesTEC study that we know that…as long as you discuss the adverse events and the patients are agreeable to it, there is superiority in giving bispecifics over some of the older regimens that we have,” she said, adding that, once treatment begins, “most patients actually love being on teclistamab.”
Cohen described how the newer data are compressing his decision-making even further. Where he once debated whether to use CAR T-cell therapy at first or second relapse, he said the strength of teclistamab plus daratumumab is “moving the CARs almost to first relapse,” because he now feels obligated to discuss a B-cell maturation antigen–directed option that early. Physicians and pharmacists alike agreed that the deciding factor is often logistics rather than efficacy: a patient’s ability to stay near the treatment center, whether a support person can help monitor at home, and comfort with a hospital stay. Hui described a patient who was reluctant to be admitted for step-up dosing, despite favorable data on daratumumab-based regimens: “Even though we know that [daratumumab] is good, our patient in the community just didn’t want to come into the hospital.”
Extending Step-Up Dosing to the Outpatient Setting
Every site represented uses teclistamab as its predominant bispecific, with talquetamab (Talvey; Johnson & Johnson) a common second option; uptake of elranatamab (Elrexfio; Pfizer) and linvoseltamab (Lynozyfic; Regeneron) remains minimal across all 5 treatment sites. How step-up dosing is delivered, however, varies substantially: Penn Medicine and Alliance Cancer Specialists (which refers to Penn for the step-up itself) do most step-up dosing outpatient, Jefferson Einstein is outpatient only, Thomas Jefferson University Hospitals uses a mix of inpatient and outpatient, and Hackensack Meridian Health remains fully inpatient. Susanibar-Adaniya described modifying the standard 48-hour interval between teclistamab step-up doses to a Tuesday/Thursday/Monday schedule so that any cytokine release syndrome (CRS) onset falls on a weekday, when full staffing is available.
Data presented on prophylactic tocilizumab—drawn from the OPTec trial and related studies—showed CRS rates dropping from approximately 50% to 70% without prophylaxis to approximately 5%, nearly all grade 1, when tocilizumab is given ahead of the first step-up dose.5 Several sites reported early difficulty getting prophylactic tocilizumab authorized because it is billed as prevention rather than treatment. Espinosa said her institution solved this by building the request into its workflow. “We have built it in our order set, in the background, for the providers to be able to be like, ‘This is going to be a patient whom I am going to use,’” she said. That way, prior authorization starts “the same time that they do teclistamab,” rather than at the last minute.
The panel also discussed which patients should not be managed outpatient. Espinosa’s criteria centered on comorbidity and support: “Especially with end-stage renal disease or heart failure, where I’m worried about the risk of CRS being higher, predominantly, those are the patients whom I admit,” along with patients who lack reliable local support during the step-up window. Cohen described similar caution for patients with amyloidosis and advanced cardiac involvement, and Hui flagged patients with underlying cognitive or psychiatric conditions that make immune effector cell–associated neurotoxicity syndrome (ICANS) difficult to assess remotely. Hui’s team is “seeing more ICANS” in such patients and struggling to distinguish it from baseline psychiatric or cognitive symptoms.
Staffing, Not Toxicity, Is the Bottleneck
Panelists returned repeatedly to a common theme: The limiting factor in scaling bispecific programs is staffing and space, not the biology of CRS or ICANS. Tasnim said her site’s constraint is physical space rather than clinical comfort.
“I wouldn’t think we need something special. For our case, our big problem is space…which is why it’s hard to accommodate some of those patients, even though it doesn’t take that much time,” she said, adding that her inpatient colleagues remain unfamiliar with recognizing CRS or ICANS if a patient presents to the emergency department (ED).
Cohen agreed that staffing was the binding constraint at Penn. “I think staffing is the key. That was the big barrier for us,” he said, describing a dedicated nurse practitioner who guides patients through step-up dosing but is “already booking out way too far and overworked.” He credited a centralized, 24/7 on-call hotline staffed by a trained, rotating pool of clinicians with transforming the program’s capacity. Patients, he said, “call this one number and you will get a trained person who knows how to manage CRS,” describing the model as having “revolutionized our ability to do the treatment.”
Chasky raised the possibility of artificial intelligence–assisted remote monitoring, describing a vendor that proposed automated check-ins with patients at home to triage symptoms before they escalate—an idea Cohen said intrigued him even as he remained skeptical that it was ready for routine use.
Building Hospital and ED Partnerships
With bispecifics now used across a growing number of tumor types—besides myeloma and lymphoma, these therapies are used in small cell and non–small cell lung cancer—panelists said community EDs will increasingly need training to recognize CRS and ICANS rather than defaulting to a sepsis workup. Hui argued that awareness, not memorization, should be the goal for ED staff: “I think trying to train them to remember how to treat CRS and ICANS is hard, so that’s where an order set or a guideline or some reference for them is useful. I think the real training is raising awareness of it and then referring them to whatever resource that is.” Espinosa described early efforts to flag patients taking bispecifics within the electronic medical record, similar to existing CAR T-cell flags, but said no consistent model has emerged across the group’s institutions. Chasky recounted a community oncologist who gave every patient his personal cell phone number while rolling out a bispecific program alone, prompting Cohen’s observation: “You need a champion.”
Payer Barriers Persist Even as Practice Moves Faster
The panel’s second half centered on a case involving a 50-year-old patient working full time with functionally high-risk R/R multiple myeloma, weighing bispecific therapy against CAR T-cell therapy and using the case to surface reimbursement friction that clinical protocols have outpaced. Panelists said Risk Evaluation and Mitigation Strategy (REMS) requirements for teclistamab have become easier to navigate than earlier REMS programs,6 though Hui noted that a recent update requiring a dispensing check with every fill has added administrative burden.
Intravenous immunoglobulin (IVIG) approval was described as inconsistent; Tasnim said her site rarely struggles to authorize IVIG, whereas Susanibar-Adaniya said she has had to submit appeal letters and switch product names before securing approval, particularly when insurers demand documentation of recurrent infection despite guideline language favoring prophylaxis. Cohen suggested clinicians submit prior authorization for IVIG at the same time as the request for a bispecific or CAR T-cell therapy. “You almost try to do it when you’re submitting for the CAR, the bispecific. You want to get the IVIG approval just so you can appeal if there’s a problem.”
On the economics of site of care, Chasky and Espinosa agreed that inpatient step-up dosing is not viable for community practices in the long term. “Inpatient step-up would be impossible, I think,” Chasky said, adding that health systems effectively absorb the cost of inpatient administration in service of recouping revenue once patients transition to outpatient maintenance dosing. Cohen said most of his patients now start entirely outpatient, receiving teclistamab first, with daratumumab added after 1 or 2 doses—a sequence chosen for billing simplicity rather than the trial’s original same-day protocol. Panelists reported few denials so far for teclistamab plus daratumumab in the second-line setting, though Cohen acknowledged uncertainty about whether insurers will eventually push back on continuing daratumumab maintenance concurrently with a new teclistamab start, a scenario not directly studied in the pivotal trial.
Scaling Bispecifics for the Second-Line Population
Closing the session, Susanibar-Adaniya pointed to the scale of the challenge to come: moving bispecific antibodies from the fourth or fifth line, where an estimated 5000 patients are eligible at each line, to the second line, where approximately 27,000 patients could qualify. With agents such as cevostamab, which targets FcRH5, and a wave of trispecific antibodies in development, along with combination approaches such as talquetamab plus teclistamab already showing high response rates in patients with extramedullary disease,7 panelists agreed the operational questions raised during the interchange—staffing, ED partnerships, prior authorization timing, and site-of-care economics—will only grow more pressing. “Teclistamab was approved at the end of October 2022, so it’s only been 4 years,”8 Susanibar-Adaniya said, “and we’re asking everybody to jump into this car, but because it’s so effective, so well tolerated, patients feel normal. So they’re able to enjoy their life, to do whatever they want. And we feel like it’s important for them to get access to this, if it’s in their best interest.”
References
- Costa LJ, Bahlis NJ, Perrot A, et al; MajesTEC-3 Trial Investigators. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. 2026;394(8):739-752. doi:10.1056/NEJMoa2514663
- Kumar SK, Callander NS, Adekola K, et al. Multiple myeloma, version 5.2026, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2026;24(1):e260001. doi:10.6004/jnccn.2026.0001
- Rosa K. FDA approves cilta-cel for R/R multiple myeloma after at least one prior line of therapy. OncLive. April 5, 2024. Accessed September 19, 2026. https://www.onclive.com/view/fda-approves-cilta-cel-for-r-r-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
- Bonavitacola J. Ide-cel receives approval for earlier treatment for relapsed, refractory multiple myeloma. AJMC. April 5, 2024. Accessed September 18, 2026. https://www.ajmc.com/view/ide-cel-receives-approval-for-earlier-treatment-for-relapsed-refractory-multiple-myeloma
- Caffrey M. Results show giving prophylactic tocilizumab reduces CRS in outpatient delivery of teclistamab, talquetamab. Am J Manag Care 2026;32(Spec 8):SP422.
- Risk Evaluation and Mitigation Strategies. FDA. May 20, 2025. Accessed September 19, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems
- Zhou S, Ke Q. Dual-targeting bispecific antibodies against extramedullary myeloma: a hypothesis-driven commentary. Transl Oncol. 2026;71:102907. doi:10.1016/j.tranon.2026.102907
- Baines AC, Kanapuru B, Zhao J, et al. FDA approval summary: teclistamab-a bispecific CD3 T-cell engager for patients with relapsed or refractory multiple myeloma. Clin Cancer Res. 2024;30(24):5515-5520. doi:10.1158/1078-0432.CCR-24-1872
