KEY TAKEAWAYS
- The MajesTEC-1 trial, a phase 1 clinical trial aimed to evaluate the safety and efficacy of teclistamab in patients with RRMM. Assessing the incidence and severity of CRS in patients receiving teclistamab and the potential of prophylactic administration.
- CRS occurred in 29% of patients, with no grade >3 CRS observed. All CRS events were successfully managed with tocilizumab without discontinuation of teclistamab.
- The patients included in the study had specific disease profiles, including ECOG score 1, ISS I/II, standard cytogenetic risk, and extramedullary plasmacytomas.
- Prophylactic administration of tocilizumab before teclistamab treatment appeared to reduce the incidence of CRS compared to the overall study population.
The first BCMA x CD3 bispecific antibody to be approved for treating relapsed/refractory multiple myeloma (RRMM) is teclistamab. In MajesTEC-1, CRS occurred in 72.1% of patients treated with the recommended phase 2 dose (RP2D) of weekly teclistamab 1.5 mg/kg (50.3% grade [gr] 1; 21.2% grade [gr] 2; 0.6% grade [gr] 3) and was successfully managed by toci in 36.4% of patients (other interventions) without affecting teclistamab response. Emerging data indicate that prophylactic administration of toci before the initial dose of bispecific antibodies reduces the incidence and severity of CRS, which could facilitate outpatient therapy initiation. This is the first prospective study to examine the effects of prophylactic toci on the incidence and severity of CRS in patients receiving teclistamab. Patients 18 years of age with RRMM who had previously received a PI, IMiD, and anti-CD38 antibody were eligible.
Patients in a prospective exploratory cohort at the RP2D or a fixed-dose fellow received subcutaneous teclistamab (following 2 step-up dosages). Toci (8 mg/kg IV single dose) was administered 4 hours before the initial teclistamab step-up dose. The CRS was graded according to Lee et al. (2014) and managed according to institutional guidelines. About 14 points were added: All patients had ECOG score 1 and ISS I/II; 91% have standard cytogenetic risk; 21% have extramedullary plasmacytomas; 31% have 30% BMPCs; median 4 prior lines of therapy (range 2–7); 64% are triple-class resistant. The median duration of follow-up was 1.2 months (range: 0.2–4.6). CRS occurred in 4 patients (29%; no grade >3 CRS); 1 patient experienced a subsequent CRS event. All events were managed with toci and resolved without teclistamab discontinuation. Around 7 of 14 patients (consistent with the overall MajesTEC-1 population) had grade 3/4 neutropenia. About 2/14 had an infection of grade 3/4. 2/14 had neurotoxicity adverse events.
About 4 from 7 response-evaluable patients responded. Cytokine and pharmacokinetic (PK) data from additional patients with extended follow-up will be presented to inform patient management. A single dose of toci administered before teclistamab treatment appeared to reduce the incidence of CRS compared to the entire MajestEC-1 study population, with no new safety signals and no evidence of an effect on teclistamab response, considering the brief follow-up. Prophylactic toci can reduce the risk of CRS in patients with disease profiles amenable to ambulatory dosing, thereby reducing the need for hospitalization during teclistamab step-up dosing.
Source: https://library.ehaweb.org/eha/2023/eha2023-congress/386740/niels.w.c.j.van.de.donk.evaluation.of.prophylactic.tocilizumab.28toci29.for.the.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
Clinical Trials: https://classic.clinicaltrials.gov/ct2/show/NCT04557098
https://classic.clinicaltrials.gov/ct2/show/NCT03145181
Niels W.C.J. van de Donk, Alfred Garfall, Lotfi Benboubker, Katarina Uttervall, Kaz Groen, Laura Rosiñol Dachs, Caroline Hodin, Tara Stephenson, Danielle Trancucci, Alfredo Perales-Puchalt, Rachel Kobos, Arnob Banerjee, Maria-Victoria Mateos/ EVALUATION OF PROPHYLACTIC TOCILIZUMAB (TOCI) FOR THE REDUCTION OF CYTOKINE RELEASE SYNDROME (CRS) TO INFORM THE MANAGEMENT OF PATIENTS (PTS) TREATED WITH TECLISTAMAB IN MAJESTEC-1 Inc, M. G. (n.d.). EVALUATION OF PROPHYLACTIC TOCILIZUMAB (TOCI) FOR THE REDUCTION OF… by Niels W.C.J. van de Donk. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386740/niels.w.c.j.van.de.donk.evaluation.of.prophylactic.tocilizumab.28toci29.for.the.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
