Introduction
While first‐line treatments recently approved in Europe have demonstrated significant improvements in outcomes for transplant‐eligible and transplant‐ineligible patients with multiple myeloma (MM), periods of response with subsequent treatment become shorter with limited treatment options for long‐term disease control [ 1 , 2 ]. Recently introduced treatment options that aim to address this challenge for patients with relapsed/refractory MM (RRMM) include T‐cell redirecting (TCR) agents, such as bispecific antibodies targeting B‐cell maturation antigen (BCMA) and G protein–coupled receptor family C, group 5, member D (GPRC5D) on MM cells [ 3 , 4 , 5 , 6 , 7 ]. These treatment options include teclistamab and talquetamab, the first approved BCMA × CD3 bispecific antibody and GPRC5D × CD3 bispecific antibody, respectively, for the treatment of triple‐class exposed RRMM [ 8 , 9 , 10 , 11 ].
Cytokine release syndrome (CRS) has been reported with bispecific antibodies, including teclistamab and talquetamab [ 5 , 12 , 13 , 14 ]. In the MajesTEC‐1 study, patients received teclistamab 1.5 mg/kg weekly (QW) with the option to switch to Q2W based on response (partial response or better after ≥ 4 cycles in phase 1 or complete response (CR) or better for ≥ 6 months in phase 2) [ 15 ]. In the MonumenTAL‐1 study, patients received talquetamab 0.4 mg/kg QW or 0.8 mg/kg every other week (Q2W), and the dosing could be reduced based on response or mitigation of side effects [ 16 ]. CRS events mostly occurred during step‐up dosing (SUD) and the first treatment cycle [ 13 , 14 ]. The risk of CRS, which is highest during the initial dosing period, can be mitigated by SUD and pre‐treatment medication (corticosteroids, antihistamines, and antipyretics) administered with each dose of the SUD schedule. Patients should be instructed to remain within the proximity of a healthcare facility and monitored for signs and symptoms daily for 48 h after administration of all doses within the SUD schedule, including the first full dose [ 8 , 9 , 10 , 11 ]. While the teclistamab and talquetamab EMA labeling guidance for the mitigation of CRS risk does not mandate hospitalization, bispecific antibodies are currently typically administered and monitored in an inpatient setting during the SUD schedule (SUD1, SUD2, first full dose) [ 17 ]. However, inpatient hospitalizations may be restricted in some hospitals with limited resources, significantly contributing to the economic burden of MM and often increasing the inconvenience for patients [ 18 , 19 ]. Furthermore, these strategies for CRS prevention and management were developed based on experience from clinical trials that included active monitoring and protocol‐mandated procedures. With increased real‐world use of bispecific antibody treatments, there is growing interest in making the administration of these agents more convenient and cost effective by exploring the potential for CRS monitoring and management in an outpatient setting (i.e., administration without overnight hospital admission).
One potential strategy is the use of prophylactic tocilizumab, which early data indicate may reduce the incidence, severity, and recurrence of CRS with bispecific antibodies. Prophylactic tocilizumab has been shown to reduce the incidence of CRS with teclistamab in the MajesTEC‐1 study, with a 65.0% relative reduction in overall incidence versus the pivotal MajesTEC‐1 population (from 72.1% to 25.0% in the prophylactic tocilizumab cohort [all events were grade 1/2]) [ 20 ]. No new safety signals (including grade 3/4 neutropenia and infection) were observed in patients receiving prophylactic tocilizumab, and there was no impact on response to teclistamab. Similar results were observed in real‐world studies in which CRS incidence was 11%–26% in patients receiving prophylactic tocilizumab with teclistamab [ 21 , 22 ]. A dedicated phase 2 prospective study, OpTec, is evaluating the impact of prophylactic tocilizumab on CRS incidence and severity in the outpatient setting, and so far, 1 of the 16 patients (6.3%) has experienced CRS, compared to 72% in MajesTEC‐1 [ 23 ]. Similarly, in MonumenTAL‐1, prophylactic tocilizumab (single dose) and increased post‐treatment dexamethasone use during SUD with talquetamab reduced the incidence and severity of CRS to 16.7%, with no grade ≥ 2 events, compared to 73.1%–79.0% in the overall MonumenTAL‐1 population [ 24 ]. Prophylactic tocilizumab had no impact on talquetamab response and did not increase the incidence of neutropenia or infections. In an ongoing phase 1 study, prophylactic tocilizumab with the Fc‐receptor homolog 5 × CD3 bispecific antibody cevostamab significantly reduced CRS incidence from 90.9% to 38.7% ( p < 0.001) [ 21 , 25 ]. Additionally, both the International Myeloma Working Group (IMWG) and National Comprehensive Cancer Network (NCCN) note the potential for prophylactic tocilizumab to reduce the risk of CRS with bispecific antibodies [ 17 , 26 ]. Overall, these data support the use of prophylactic tocilizumab for the prevention of severe CRS as well as for the safe administration of bispecific antibodies in an outpatient setting [ 21 , 22 , 23 , 27 , 28 ].
There is also initial evidence to support the use of prophylactic dexamethasone to reduce the incidence and severity of CRS. A US single‐center study demonstrated that an outpatient monitoring program in patients receiving prophylactic dexamethasone on the day after each SUD may be effective, reducing the total number of hospital days from 116 to 19 [ 29 ]. Although 4 of the 18 patients were admitted to hospital due to grade 2 CRS, there were no cases of serious CRS or ICANS. As expected, the addition of dexamethasone led to related toxicities, including hyperglycemia (4 patients), hypertension (3 patients) and insomnia (1 patient). While precautions do need to be taken with patients who have specific comorbidities, this remote monitoring program substantially reduced the total number of days in hospital for this cohort. Furthermore, a retrospective analysis of patients receiving teclistamab among six US academic medical centers showed that patients experiencing grade 1 CRS may be safely treated with as few as one dose of dexamethasone 10 mg, which may allow patients with low‐grade CRS to be managed in an outpatient setting by preventing unwarranted hospital admissions [ 30 ].
Therefore, emerging data support the feasibility of teclistamab and talquetamab administration in an outpatient setting with close monitoring for AEs, such as CRS, which is already ongoing in several centers. Under the Mayo Clinic hospital‐based outpatient program, remote monitoring kits are provided for patients to manually measure vital signs regularly and check for signs and symptoms of CRS and immune effector cell–associated neurotoxicity (ICANS) during the SUD schedule [ 31 ]. At Fox Chase Cancer Center, eligible patients were required to remain within 1 h of a hospital with a caregiver for 10 days after SUD and received education about the signs and symptoms of CRS and ICANS, daily outpatient clinic evaluations, home‐based vital sign monitoring, and regular physician phone calls [ 32 ]. Within the French Early Access Program, eight patients were dosed exclusively in an outpatient setting, with at‐home monitoring by a nurse; only one patient required an unplanned admission to the hospital to manage grade 2 CRS and cytomegalovirus reactivation. Outpatient teclistamab SUD is feasible based on this experience with careful patient selection and monitoring close to home [ 33 ].
While early data and experience indicate outpatient administration of bispecific antibodies is feasible, there is a lack of guidance on implementing this type of administration in European clinical practice. Furthermore, hematology treatment protocols, access to supportive care, and hospital, clinic, and outpatient structures vary across Europe. We therefore conducted an expert consensus survey among a panel of European physicians specializing in MM to evaluate the current and future application of outpatient administration of teclistamab and talquetamab in clinical practice. This consensus survey aimed to provide a cohesive, clinically relevant overview of current experience and expert recommendations with outpatient administration of teclistamab and talquetamab.
Methods
Expert Panel
Drs. Lund, Khandanpour, and Perrot formed the steering committee, which helped to identify selection criteria for the expert panel and contributed to the development of the survey. Ten physicians with expertise in the treatment of MM from different geographic regions across Europe were nominated based on clinical experience with bispecific antibodies and an interest in outpatient treatment. The experts were from both academic and non‐academic centers based in Austria, Belgium, Denmark, France, Germany, Italy, Spain, Sweden, and the Netherlands. Nearly all (8/10) experts have dedicated at least half of their professional activity to patients with MM, and all have experience treating patients with teclistamab and talquetamab. Four experts already had individual experience treating patients with these bispecific antibodies in an outpatient setting during SUD at their centers.
Survey Development
The steering committee led the development of a survey based on expert consensus methodology. The survey was developed in a stepwise collaborative approach: the first version was developed with the steering committee in June 2024; this was followed by a review of the survey with all expert panel members in July 2024 before the survey was finalized. The survey was designed to focus on outpatient treatment with teclistamab or talquetamab in Europe, feasibility of SUD and maintenance treatment, patient eligibility, monitoring and management (including CRS, ICANS, and infection), potential benefits and limitations, and anticipated changes in future practice. The survey was distributed via the SurveyMonkey platform. Responses were not submitted anonymously in order to take into account country and center specifics. After all experts had completed the survey, the answers were openly discussed during the consensus meeting. The full survey is shown in Supporting Information S1 : Table 1 .
The electronic survey was distributed in July 2024. All expert panel members were requested to answer 17 survey questions and provide qualitative feedback where appropriate. Answers were discussed and clarified during a 1‐h follow‐up telephone call with each of the panel members.
Expert Consensus Meeting
Following survey completion, the expert panel members participated in an online consensus meeting in September 2024 to review the responses to each question collectively, align on areas in which a clear consensus remained to be reached based on the survey responses, and gather more detailed, practical insights into evolving outpatient administration practices. This meeting was facilitated by the Metaplan Moderation Method to allow for a structured dialogue between experts, stimulate the active participation of each member, and ensure a detailed discussion to reach a consensus position. The experts first discussed how consensus would be measured for the purposes of the meeting. All experts agreed that consensus was considered to have been achieved if ≥ 60% of the expert panel chose the same answer; strong agreement was considered to have been reached if ≥ 80% chose the same answer, while disagreement was represented by < 60% choosing the same answer.
The 3‐h online meeting was held in September 2024 and reflected the expert panel opinions and experience at that time. The results presented in this paper comprise the collated responses to each of the survey questions from the online survey, follow‐up call, and consensus meeting.
Results
Definition of Outpatient Settings and Community Centers
There are various outpatient treatment settings across European countries (Supporting Information S1 : Table 1 [Q3]). Given the heterogeneity of MM clinical practice, the expert panel members defined “outpatient” as any healthcare service not requiring an overnight stay in a healthcare delivery institution. The terms “outpatient department,” “outpatient clinic,” “day clinic,” or “day hospital” were considered to refer to the hospital department intended for outpatient treatment within specific opening hours and could exist at both academic and non‐academic centers. “At home” administration was also discussed as part of the OPD definition, although experience and guidance were limited.
Benefits and Limitations of Outpatient Administration
The main benefits of outpatient administration are expected to be saving hospital capacity, saving time for patients (depending on center protocols), and providing patients with a more comfortable experience when receiving bispecific antibodies (Supporting Information S1 : Table 1 [Q4]). Physicians or a specialized nurse familiar with CRS, ICANS, and infections would still need to be on call to support outpatient administration where needed. Cost‐effectiveness is also expected to be a benefit of outpatient administration of teclistamab and talquetamab, but would need to be demonstrated through real‐world economic analysis and/or modeling studies.
The main barriers to outpatient administration are anticipated to be fear of serious AEs and a lack of knowledge about AE management; however, these barriers should be overcome or minimized as countries and local centers gain experience with teclistamab and talquetamab (Supporting Information S1 : Table 1 [Q5]). Physicians need to gain experience in AE management with inpatient administration and ensure the needed resources and infrastructure are in place before establishing a protocol and implementing outpatient administration. While preliminary data support outpatient administration with bispecific antibodies [ 23 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], published data on outpatient experience is still limited; recent studies (including the phase 2 OpTec study) [ 23 ] and real‐world evidence [ 22 ] will play an important role in building physician and healthcare authority confidence in outpatient administration. Some countries (including Austria) require these data to assess reimbursement eligibility. Saving time and capacity should be a sufficient economic benefit for outpatient administration. Efficient and economically viable processes will therefore need to be established—both at a country and local center level—to support outpatient administration effectively.
Current Treatment Practice During SUD
While there was strong agreement among experts that outpatient administration of teclistamab and talquetamab during SUD is feasible, it is not routinely used and is currently practiced only in approximately 40% of European countries (Supporting Information S1 : Table 1 [Q1 and Q2]). The heterogeneity of hematology practices across countries and centers may be due to a lack of experience and confidence with this type of administration, although it is anticipated that some countries will transition to an outpatient setting over the coming months as experience in inpatient settings increases. Sharing experiences and best practices across Europe may help reassure healthcare professionals (HCPs) in less‐experienced countries of the feasibility of this approach for patients with MM.
For centers currently administering teclistamab and talquetamab, the usual teclistamab SUD schedule is either days 1–3–5 or days 1–4–8. The 1–3–5 schedule is often favored; however, the 1–4–8 schedule allows patients the flexibility and freedom to receive treatment on either side of the weekend (Monday or Friday) and is more supportive of treatment in an outpatient setting, given such departments are usually closed over the weekend. For talquetamab, the SUD schedule is either days 1–3–5 for QW or days 1–3–5–7 for Q2W administration, with clinicians generally favoring the Q2W schedule. As the risk of CRS decreases with each exposure, the longer schedules may allow consideration of outpatient management beginning with the last SUD injection of teclistamab or talquetamab (i.e., day 8 or 7, respectively). In terms of future preferred SUD schedules, experts strongly agreed that current inpatient schedules would also apply to an outpatient setting (Supporting Information S1 : Table 1 [Q6]).
Outpatient administration of teclistamab and talquetamab is considered feasible across Europe, although there may be a lack of support and/or reimbursement in some countries. To adopt outpatient administration of teclistamab and talquetamab during the SUD phase, a robust and effective infrastructure is needed. There was strong agreement among experts that a day hospital in an expert center or community center could manage SUD administration of teclistamab and talquetamab (Supporting Information S1 : Table 1 [Q3]). In some countries, community hospitals already treat a high volume of patients with MM and, therefore, have considerable expertise and robust logistical procedures in place (including emergency department/intensive care unit [ICU] access). In non‐expert centers, experience first needs to be gained in administering these treatments in an inpatient setting. In some countries (such as Germany), outpatient SUD could be administered at the physician's office or private practice, provided they have a cooperative relationship with a larger hospital that has an ICU and related infrastructure.
Defining the Eligible Patient Population for Outpatient SUD
For the successful management of SUD in an outpatient setting, it is important to consider key criteria that define patient eligibility. There was strong agreement among experts that these should include cognitive status, low tumor burden, well‐controlled comorbidities, patients residing within 30–60 min of the hospital, and the presence of a reliable caregiver residing at the same home, patient fitness, patient willingness to consider outpatient management, age, and HCP presence (Figure 1 and Supporting Information S1 : Table 1 [Q7]). A difference in eligibility criteria for outpatient SUD administration between teclistamab and talquetamab is unlikely.
Cognitive status was considered a key criterion. Only patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) score < 3 should be considered for outpatient SUD. The patient's ability to take necessary action in case of AEs will also be an important factor.
A low tumor burden may be a less significant criterion than cognition when assessing outpatient SUD eligibility. While the risk of severe CRS is often considered to be higher for patients with high tumor burden, this has not been confirmed in clinical trials of bispecific antibodies, and the risk is generally lower than that associated with other therapies (such as chimeric antigen receptor T‐cell therapies).
Comorbidities should be well‐controlled, and patients should also be checked for active infections when considering outpatient administration. Comorbidities and age are usually linked to fitness, which should also inform eligibility, and the age‐adjusted frailty score could be used.
Distance and/or travel time to a hospital should also be taken into consideration when assessing patient eligibility for outpatient SUD. Patients in densely populated areas are more likely to live within an acceptable distance of a hospital than patients in rural areas, but the potential for slow travel through a city during busy periods should be considered. Patients living within a 30‐ to 60‐min commute to a hospital would likely be considered eligible for outpatient SUD. Moreover, the presence of a caregiver residing in the same home as the patient is likely to be mandatory because of the potential risk of developing CRS, neurotoxicity, or ICANS while on treatment, which may impair the patient's cognitive status. A caregiver can be educated to recognize relevant signs and symptoms and can take the patient to a hospital if needed. Regular HCP (i.e., nurse) visits to a patient's home during the SUD phase are less likely to be an additional support to facilitate outpatient treatment.
Specific eligibility criteria are detailed in the expert consensus framework (Figure 1 ). It is important to note that eligibility criteria will likely evolve as centers and countries gain experience in outpatient SUD administration, and this may provide more flexibility in terms of fitness thresholds, caregiver presence, and distance from a hospital.
Considerations Before Starting SUD in an Outpatient Setting
Promising initial data indicate preemptive tocilizumab is associated with a reduction in CRS incidence (~25% compared with ~70%) and severity (almost all cases grade 1/2), with no observed impact on treatment efficacy [ 20 , 21 , 24 , 25 , 27 ]. However, there are likely to be mixed opinions in practice on whether tocilizumab should be used preemptively to prevent CRS during outpatient SUD (Supporting Information S1 : Table 1 [Q8]). Tocilizumab also has a long duration of action (~10–15 days), which spans the SUD phase [ 20 ], reassuring HCPs that recurrent CRS events during this period may be mitigated. However, tocilizumab is not reimbursed in the prophylactic setting in some countries (e.g., Germany, Italy, Austria, Spain, and Belgium), and preemptive use could be considered off‐label. Furthermore, inpatient experience with bispecific antibodies has demonstrated that severe CRS/ICANS events are infrequent, and systematic preemptive tocilizumab for all patients might be considered overtreatment by some. Overall, the lack of randomized trial data and economic analysis assessing tocilizumab prophylaxis represent potential limitations for the use of tocilizumab in this setting.
However, there is more uncertainty surrounding the preemptive use of dexamethasone as an alternative to tocilizumab (Supporting Information S1 : Table 1 [Q9]). While it could be useful in patients at particularly high risk of CRS or with increased tumor burden, it may be considered overtreatment to use in all patients receiving bispecific antibodies. Arguments against preemptive dexamethasone use include its immunosuppressive nature and corresponding infection risk [ 40 ]. Furthermore, data demonstrating the benefit of additional dexamethasone during CRS and published guidelines on this approach are still lacking. Dexamethasone may also be less effective than tocilizumab at preventing CRS, particularly recurrent CRS events [ 14 ].
To avoid under‐ or overtreatment with either preemptive tocilizumab or dexamethasone, a predictive model could be developed to estimate CRS risk.
It will be vital that cases of CRS, ICANS, and infections are monitored and managed effectively during outpatient SUD administration of teclistamab and talquetamab. While some monitoring and management approaches will likely be mandatory, others may be beneficial but not essential for effective outpatient management. Only centers with easy access to a hematology department or a hematologist familiar with CRS, ICANS, and infections, an emergency department, and/or an ICU should consider outpatient administration of teclistamab and talquetamab (Supporting Information S1 : Table 1 [Q10 and Q12]). While expert/academic centers likely already satisfy these requirements, many community centers may do so as well. In Germany, for example, smaller centers or private practices with established connections to larger centers could arrange access to these services.
Patients will play an important role in monitoring and managing AEs during outpatient SUD administration. Patients should ensure that they can reach the hospital in sufficient time if needed and should have a caregiver who resides in the same home. Patients and caregivers will need to have a good understanding of what to do in case of AEs; patient willingness to receive simple training and education around AE monitoring will be vital for the successful management of AEs. To help facilitate this, patient/caregiver education, including patient notices and patient cards, should be simple to understand and should clearly explain the signs and symptoms of CRS and ICANS (Supporting Information S1 : Table 1 [Q10]). After receiving education, the treating physician should be confident that the patient is “reliable,” can effectively monitor AEs, and will contact the on‐call hematologist if they experience signs and symptoms of AEs. Mandatory premedication will also be vital in the management of AEs during outpatient SUD with teclistamab and talquetamab.
Protocol for SUD in an Outpatient Setting
The importance of a robust protocol for outpatient administration of bispecific antibodies should not be underestimated. An example of a protocol for teclistamab outpatient administration already used by the Cancer University Institute of Toulouse (IUCT) in France is described in Supporting Information S2 : Table 2 . Alongside patient selection considerations, this protocol describes the HCP notice, patient notice (shared with the patient's general practitioner and private nurse as well as the patient), and the teclistamab patient card. The IUCT protocol was used by the expert panel members as a basis for the developed consensus framework (Figure 1 ), which can be adapted by centers across Europe to develop local protocols for the outpatient administration of teclistamab and talquetamab.
During the SUD phase, patients or caregivers must monitor temperature, blood pressure, and oxygen saturation two to three times a day. It is therefore recommended that patients are provided with a prescription in advance for a thermometer, blood pressure monitor, and pulse oximeter (Supporting Information S2 : Table 2 ). In terms of the minimum equipment a patient should have at home for CRS, ICANS, and infection monitoring, experts agreed that a thermometer and blood pressure monitor should be available to all patients being treated in an outpatient setting (Supporting Information S1 : Table 1 [Q11]). While a pulse oximeter and/or immune effector–cell encephalopathy testing may be useful, they may not be considered mandatory. A monitoring application to record symptoms is unlikely to be useful, as continuous monitoring is not considered necessary and could increase patient anxiety (Supporting Information S1 : Table 1 [Q11]).
In terms of other CRS management approaches, there was strong agreement among experts that outpatients should be given a prescription of paracetamol and dexamethasone (in case of fever refractory to paracetamol). The duration of action of dexamethasone (~40 h) could be useful in managing the patient's symptoms prior to arrival at a hospital, where they could then receive tocilizumab. In countries where preemptive tocilizumab is not possible, dexamethasone is a feasible alternative, and dexamethasone prescriptions should reassure HCPs that CRS emergencies are rare in patients with MM receiving bispecific antibodies. Some experts felt it was sufficient to advise patients who develop a fever at home to take paracetamol and go to a hospital. If patients develop signs and symptoms of grade 2 CRS, the anticipated prescription of dexamethasone can be taken following telephone instructions from the on‐duty onco‐hematologist. If needed, either the onco‐hematologist on duty or a specialist nurse should be the first person to be contacted by outpatients during the SUD phase. Ideally, a specialist nurse would be available to screen patients before contacting the onco‐hematologist on duty. It would probably not be useful for patients to call their general practitioner or private nurse when experiencing AEs during the SUD phase, as they would not necessarily be knowledgeable about AEs associated with bispecific antibody treatment.
Current Treatment Practice During Maintenance Dosing
While home administration of teclistamab and talquetamab following the SUD phase (i.e., treatment maintenance) is not yet routine practice in Europe, this would help address ongoing inpatient capacity issues across the region. Patients receiving bispecific antibodies typically experience fewer AEs during the maintenance phase than the SUD phase, and current at‐home treatment administration procedures used for other MM therapies could be applied to teclistamab and talquetamab treatment.
Home administration is already practiced in some European countries during the maintenance phase for bortezomib, carfilzomib, daratumumab, and isatuximab, with bortezomib and daratumumab being the most frequently administered using this method.
Experts strongly agreed that patients receiving teclistamab or talquetamab are already routinely transferred from expert centers to community centers for maintenance phase treatment, with strong connections between the two center types existing for such purposes (Supporting Information S1 : Table 1 [Q15]). Patients could potentially be transferred to community centers at cycle 2 or 3, given that patients would be in the maintenance phase of treatment and published guidelines exist for managing patients receiving bispecific antibodies (e.g., IMWG and European Myeloma Network guidelines) [ 17 , 41 ]. As more community centers gain experience with teclistamab and talquetamab, this approach may be more likely to evolve into common practice. As community hospitals become better equipped to handle the SUD phase, there may in turn be a reduced need to initiate treatment in a hospital‐based setting and then transfer patients in the future.
In some countries (e.g., Denmark, Spain, France, Belgium, and the Netherlands) logistics are already in place to support this type of administration and outpatient administration is routine for other MM treatments (e.g., daratumumab, bortezomib, and carfilzomib).
While it is important to acknowledge that there will be differences in practice among countries, there was strong agreement among experts that a day hospital in either an expert center or community center could manage maintenance administration of teclistamab and talquetamab (Supporting Information S1 : Table 1 [Q3]). Physicians may also consider transferring patients from a day hospital to home administration if feasible. This could be done shortly after the SUD phase or at the beginning of cycle 2, given the likely lower risk of CRS after the SUD phase.
Anticipated Changes in Administration Practice
It is highly anticipated that there will be increased adoption of teclistamab and talquetamab outpatient treatment across Europe in the future (Supporting Information S1 : Table 1 [Q16 and Q17]). This is particularly expected in the context of outpatient treatment during the SUD phase within a day hospital. Clarity on country‐level regulations and guidelines will be essential for the effective adoption of outpatient administration of these bispecific antibodies during the SUD phase.
As many as 50% of patients receiving teclistamab or talquetamab may be treated in an outpatient department during the SUD phase within the next 3 years. This proportion of patients could be higher in some countries (e.g., France) (Supporting Information S1 : Table 1 [Q17]). However, it is expected that at least 20% of patients will likely need to be treated as inpatients if they are at high risk of complications (e.g., due to comorbidities).
In the near future, a lower proportion of patients is expected to receive teclistamab or talquetamab at home during the maintenance phase within the next 3 years. The proportion of patients receiving maintenance treatment at home will vary by country, depending on the structures in place to support this type of administration, the perceived need for it, and the level of similar experience with other MM treatments.
Discussion
The outpatient experience in hematology practice in general, and with bispecific antibody treatment in particular, is highly heterogeneous across European countries. While for some countries (e.g., France) administration of teclistamab and talquetamab in an outpatient setting is already practiced for eligible patients with MM, for others (e.g., Germany and Austria), this type of administration is challenging in the context of existing healthcare policies and infrastructure. However, these differences may be due to a lack of experience and confidence in outpatient administration. Sharing of best practices (e.g., guidelines and training programs) by countries with more experience will help to reassure HCPs and will provide evidence for the feasibility of this type of administration.
Overall, the outpatient administration of teclistamab and talquetamab during the SUD phase is considered feasible and is expected to provide benefits to patients and healthcare centers. It is important that HCPs and individual centers first gain experience in treating inpatients with bispecific antibodies before treating outpatients. Many departments already transfer patients from expert hospitals to community hospitals/centers, supported by the recent publication of peer‐reviewed guidelines on bispecific antibody treatment, particularly AE management. Patients' cognitive status, fitness, and caregiver presence are essential considerations when assessing outpatient eligibility, as reflected in the proposed framework developed by the authors (Figure 1 ). In some countries, the infrastructure already exists to support outpatient administration of other MM treatments (e.g., daratumumab) during the maintenance phase, which could be applied to teclistamab and talquetamab. Indeed, it is feasible that, in some countries, home administration of bispecific antibodies during the maintenance phase could be performed by a nurse associated with a hospital; however, this practice is still limited. Other factors enabling outpatient administration in the future will include patient autonomy and willingness, the presence of a caregiver, and physician confidence in safety (Supporting Information S1 : Table 1 [Q14 and Q17]).
Additional evidence from clinical trials, such as OpTec conducted in the US and a Canadian pilot study ( NCT06251076 ), in addition to real‐world practice will be important in defining key aspects of outpatient administration across each treatment phase for teclistamab and talquetamab, including prophylactic use of tocilizumab and dexamethasone. If prophylactic tocilizumab is one strategy that may support implementation of outpatient teclistamab, the addition of dexamethasone for CRS management may also serve as an effective method for outpatient teclistamab administration. For practices without immediate access (logistically or financially) to tocilizumab, the use of dexamethasone may prevent unwarranted admissions and allow patients with low‐grade CRS to be managed in an outpatient setting.
Sharing of best practices—such as training programs and standard operating procedures (SOPs; e.g., the IUCT protocol [Supporting Information S2 : Table 2 ]) – will be instrumental in providing guidance to HCPs in countries less experienced in outpatient administration and supporting patients in self‐monitoring. Although further research is needed, outpatient administration has the potential to avoid hospital admission and costly resource utilization. A small US‐based study demonstrated cost savings for an outpatient‐based practice for bispecific antibody administration [ 42 ]. However, the economic impact of outpatient administration is likely to vary between countries and even centers in the same country. Consequently, more robust EMEA‐driven economic analyses (in both the SUD and maintenance phases) will be essential in demonstrating the benefits of this approach and enabling its adoption in clinical practice.
Although there are currently barriers to the outpatient administration of bispecific antibodies in an outpatient setting, these can be managed and/or overcome with clinical experience, best practice sharing, and robust SOPs. Ultimately, outpatient administration has the potential to improve patients' experience and to support HCPs in more effectively managing larger cohorts of patients with constrained resources. The expert panel hopes that sharing this consensus framework will provide robust guidance to centers across Europe, allowing them to replicate the described methodology to create their own protocol—for both current and future bispecific antibody treatments—and to feel more confident managing patients with MM in an outpatient setting. Local pilot programs can also be considered and used to establish and refine outpatient administration protocols. Ultimately, the development of standardized European guidelines will be instrumental in harmonizing local frameworks, facilitating a uniform approach among countries, and influencing the evolution of local healthcare policies.
Author Contributions
All authors contributed equally and had access to the survey outputs, discussions, and meeting report. All authors reviewed the manuscript and approved the final version for submission.
Ethics Statement
Ethical approval was not sought for the present study because it reports the results of a survey of clinicians and did not involve any direct interaction with human or animal subjects. Therefore, it was deemed exempt from ethical review by an institutional review board.
Conflicts of Interest
Cyrus Khandanpour has received honoraria for speaker bureau and advice from Amgen, BeiGene, BMS, Johnson & Johnson, Oncopeptides, Pfizer, Stemline, and Takeda. Maria Theresa Krauth has received honoraria and/or attended advisory board meetings for AbbVie, Amgen, BMS/Celgene, GSK, Johnson & Johnson, Oncopeptides, Pfizer, Sanofi, Stemline, and Takeda. Matthieu Javelot, Claire Albrecht, and Cristina Entrala Cerezo are employees of Johnson & Johnson.
Supporting information
Table S1. The 17‐question survey and summary of expert responses.
Table S2. Teclistamab outpatient administration protocol used by the Cancer University Institute of Toulouse (IUCT), Toulouse, France.
Acknowledgments
Panel members provided written informed consent and were paid an honorarium in recognition of their time and relative contributions to developing/responding to the survey and participation in a subsequent expert consensus meeting. Support with the survey and online consensus meeting was provided by Claire Terrington from Metaplan. Medical writing support was provided by Amy Bray of Eloquent Scientific Solutions.
Lund T., Khandanpour C., Anguille S., et al., “European Expert Panel Consensus on Outpatient Administration of Teclistamab and Talquetamab in Patients With Multiple Myeloma: Feasibility, Key Considerations, and Future Directions,” European Journal of Haematology 115, no. 4 (2025): 358–366, 10.1111/ejh.14444.
Funding: This work was supported by Johnson & Johnson Global Services LLC.
Data Availability Statement
The survey results supporting the findings of this study are available within the article and its supplementary material.
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Associated Data
Supplementary Materials
Table S1. The 17‐question survey and summary of expert responses.
Table S2. Teclistamab outpatient administration protocol used by the Cancer University Institute of Toulouse (IUCT), Toulouse, France.
Data Availability Statement
The survey results supporting the findings of this study are available within the article and its supplementary material.