Background. Bispecific antibodies represent a novel valid therapeutic approach for heavily treated relapsed/refractory multiple myeloma (RRMM) patients. Key adverse events include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Guidelines for optimal use of bispecific antibodies in MM are available from the IMWG Immunotherapy Committee (Rodriguez-Otero et al., 2024). In the MajesTEC-1 study 72.1% of patients experienced CRS and, in a cohort of 24 patients, tocilizumab (anti-IL-6 receptor antibody) reduced the risk of CRS when administered prior to the first step up dose. Only a few real-world studies have recently confirmed these observations and prophylactic use of tocilizumab is still considered investigational in Italy.

Aim. The aim of the study was to assess the impact of prophylactic tocilizumab on the incidence of CRS and ICANS in RRMM patients treated with bispecific T-cell engagers in inpatient and outpatient settings in our institution.

Methods. We retrospectively evaluated patients with RRMM treated with T‐cell redirection agents outside of clinical trials at our center between 2023 and 2025. We included patients who completed the step up dose phase and received at least one treatment dose, focusing on baseline characteristics, different kinds of premedication and rates of CRS, ICANS and other adverse events (AE).

Results. A total of 23 patients were identified, including 3 patients who received sequentially 2 different bispecific antibodies, resulting in a total of 26 step up dose phases. Median age of patients was 65.5 years. Patient had received 3 to 8 (median 5) prior lines of therapy and all patients were triple class exposed. Twelve patients (46%) had received previous anti-BCMA therapy (8 belantamab, 2 both belantamab and teclistamab, 1 teclistamab and 1 idecel). Talquetamab was administered to 16 patients (61%), teclistamab to 8 (30%), elranatamab to 2 (8%). A total of 23 out of 26 step up doses were administered in hospital setting, with median time of hospitalization of 9 days (range 8-18), while 3 step up doses were administered in an outpatient setting. Premedication for each step up dose included dexamethasone, acetaminophen and diphenhydramine. In 15 step up dose phases (58%) prophylactic tocilizumab at the dose of 8mg/kg was administered prior to the first priming dose. The 3 patients treated in the outpatient setting, in addition to prophylactic tocilizumab, also received a preventive dose of dexamethasone during all the step up dose phase. CRS was reported in 46% of patients, mostly after the first step up dose (75%) and they were all grade 1. None of the 3 patients treated in the outpatient settings developed CRS. Four patients experienced more than one event of CRS during the step up dose phase. CRS treatment included tocilizumab in 9 patients (75%), for those who did not receive it as prophylactic strategy, dexamethasone in 4 patients (33%) and paracetamol alone in 5 (42%). CRS rate was significantly lower in patients who receive tocilizumab as prophylactic strategy (p 0.0447), whereas no other statistically significant differences in CRS incidence were observed across patient subgroups stratified by disease burden or laboratory parameter. Patients who developed CRS events had a significant longer time of hospitalization (median 13 vs 8, p= 0.00092). ICANS, all grade 1, was observed in 2 patients (8%). Thrombocytopenia and neutropenia were the most common haematological toxicities, reported in 57% and 46% of patients respectively, but did not affected the course of treatment, since only in one case therapy was postponed because of haematological toxicity. With a median follow-up of 2 months, we evaluated the overall response rate (ORR) in 19 out of 26 treatments: ORR was 84% and it was not affected by prophylactic tocilizumab.

Conclusion. Although the small sample size of our cohort,we observed that prophylactic use of tocilizumab was associated with a reduced incidence of CRS and consequently with a significative reduction of days of hospitalization, with no impact on ORR. This data supported, in our center, the use of prophylactic tocilizumab in outpatient setting. Given these results, even if all CRS events were grade 1, remained fully manageable and ICANS were rare, the use of prophylactic tocilizumab could improve treatment safety, inpatient management, and ultimately support feasibility in the outpatient regimen.

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2025
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