French Monocentric Experience of Outpatient Step-up Dosing of Teclistamab in Relapsed Refractory Multiple Myeloma
Authors: Hebraud Benjamin , Granell Miguel , Lapierre Leopoldine , Mouchel Pierre Luc , Beziat Guillaume , Sicard Nina , Bonneau Maeva , Higue Jules , Sougy Florence , Perriat Sophie , Morel Charlotte , Bories Pierre , Corre Jill , Avet Loiseau Herve , Recher Christian , Perrot Aurore 
Published: December 2023

Background
Teclistamab is the first approved BCMAxCD3 bispecific antibody for relapsed/refractory multiple myeloma and is available in France since October 2022 through a procedure facilitating patient access to innovation addressing high unmet medical needs (Acces Precoce, AP). Given specific toxicities, associated with novel bispecific therapies, including cytokine release syndrome (CRS), inpatient step-up dosing is usually considered. However, the favorable toxicity profile of teclistamab may be conducive to outpatient administration. Our center is already experienced in outpatient stem cell transplantation for newly diagnosed transplant eligible myeloma patients. Here, we report the characteristics and outcomes of patients treated with teclistamab exclusively in an outpatient setting, including the step-up dosing phase.
Methods
Among the 32 patients who completed the step-up dosing schedule of teclistamab in our center between January 2021 and July 2023, 15 were treated outside of clinical trials and 8 patients received teclistamab exclusively in an outpatient unit. Eligibility for outpatient step-up dose administration was based on (1) clinical and (2) logistical criteria: 1) general condition maintained, no active infection, no high tumor burden or very rapidly progressing disease; 2) patient agreeing to stay within 30 minutes of transportation to the site for 48 hours after each step-up dose and after the first full dose. The 8 eligible patients underwent specific monitoring at home: consisting of measurement of temperature, blood pressure and oxygen saturation by a homecare nurse twice a day for 15 days. Patients and careers were trained in self-monitoring of the CRS and were provided with a blood pressure monitor and an oxymeter. In addition to the regulatory documents of the French AP, patients were given a practical drug information sheet. Oral dexamethasone was available at home in case of emergency with hospital 24-hour contacts in the event of grade ≥ 2 CRS or any other complication.
Results
In addition to one patient treated in the MajesTEC3 trial, 7 of the 15 patients treated outside clinical trials since January 2023 (47%) were dosed exclusively in outpatient setting. Median age was 69 years (43-81). Isotype of myeloma was FLC in 5/8 patients. Teclistamab was given after a median of 4 previous lines of therapy (3-7). Dose escalation was carried out in accordance with FDA and EMA recommendations after premedication with dexamethasone. CRS was reported in 3 patients (2 grade 1, 1 grade 2 treated with dexamethasone and tocilizumab). No ICANS or infections G ≥ 2 were reported. ORR was VGPR or better in the majority of the patients (6/8). To date, only one patient required an unplanned admission, of 10 days to manage both grade 2 CRS and CMV reactivation occurred simultaneously. There were no toxicity-related deaths. According to local procedures, all the patients received prophylaxis with antibiotics and antivirals as well as polyvalent immunoglobulins. Cost analysis is ongoing and all the data will be updated at the time of the presentation.
Conclusion
Outpatient teclistamab step-up dose is feasible with careful patient selection and close at home monitoring, and seems associated with similar safety profiles and efficacy outcomes as inpatient treatment. Outpatient management is cost-effective and may help optimize healthcare resource utilization.