The Italian scenario for triple-refractory multiple myeloma (MM) patients has recently started to undergo a radical revolution with the introduction of CAR-T and bispecific antibodies (BSAbs), offering to this population significantly higher survival rates. However, these medicines are characterized by some pathognomonic side effects, such as cytokine releasing syndrome (CRS) and Immune Cell Associated Neurologic Syndrome (ICANS), which must be managed in a multidisciplinary manner. Regarding BSAbs, three aspects must be considered: they can be administered also outside CAR-T accredited hub centres, the severity and frequency of CRS and ICANS are lower than CAR-T, the patients are commonly hospitalized during step-up doses (SUD) due to the higher frequency of CRS and ICANS.

Given the outstanding efficacy of these drugs, their likely increasing use and the constant shortage of inpatient availability, in this retrospective real-world study we evaluated the safety and real-life feasibility of BSAbs administration in an outpatient setting in two centres in Italy, one of which is CAR-T accredited, highlighting any challenges to be addressed. Among MM candidates to BSAbs according to labelling, patient selection for outpatient management was based on i) being eligible for outpatient SUD treatment; ii) being independent or having with a caregiver; iii) absence of high disease burden (rapid progression, extramedullary disease) or severe comorbidities, especially respiratory. Educational materials regarding CRS and ICANS was distributed to patients, management algorithms and training courses were administered to emergency room doctors, neurologists, resuscitators and nurses, creating a ‘preferential’ pathway for access to the emergency room for these patients. A special attention was given to patient education: in case of fever, they were instructed to take paracetamol at home and to go directly to the haematology ward, in case of persistent fever or appearance of hypotension or desaturation, they were instructed to access to emergency room, where they were treated in collaboration with the haematologist on call. Finally, the proximity of the patient to the centre was considered: for those living more than 30 minutes away from the centre, in collaboration with charities, free apartments were provided in the hospital proximity, and were equipped with a sphygmomanometer, pulse oximeter and thermometer to monitor vital signs several times a day. All patients underwent premedication with acetaminophen, chlorphenamine and dexamethasone during SUD and first full dose whereas three patients received post-medication with dexamethasone 16 mg the day after SUD1, SUD2 and first full dose. The SUD schedule was generally d1, d4, d8, with variability depending on logistical requirements or possible postponement of the next SUD in case of CRS.

We therefore collected data on 8 patients with MM treated with BSAbs from 10 October 2024 to 22 July 2025 with a median age of 70 years, 5 of which were treated in fourth line, 2 in fifth line and one patient in seventh line. Seven patients were treated with teclistamab and one with talquetamab, approved after teclistamab in Italy. Only 2 patients experienced CRS, both of grade 1 the day after the first SUD. After the first temperature rise, patients took acetaminophen at home and they were instructed, in case of unresponsiveness to acetaminophen or appearance of other symptoms, to go to the Hematology Department during the day or to the emergency room at night or on weekends, where they could be managed. For both these two patients, tocilizumab was administered with rapid resolution of CRS and no need of hospitilization. No ICANS were observed in the 8 patients. Post-medication was not administered to 5 of the 8 patients, without increasing of CRS o ICANS rate.

Despite the limited number of patients included in this study, the experience of managing MM with BSAbs as outpatients is increasing and an ease of use was noticed even for patients with a higher disease burden for which patients were initially hospitalized for SUD. A solid collaboration with emergency room doctors and nurses, the education of the patient and the outline of a path to rapidly and safely manage complications has been documented to be crucial. These encourage the feasibility of managing BSAbs therapy for MM patients in an outpatient setting in hub centres where multidisciplinary collaboration can be easily achieved.

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2025
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