MajesTEC-1 Update Shows Tocilizumab to Reduce CRS With Teclistamab in RRMM

Niels W.C.J van de Donk, MD, PhD

A study presented at the 2024 American Society of Clinical Oncology (ASCO) meeting found that adding tocilizumab (Actemra) to teclistamab-cqvy (Tecvayli) treatment significantly reduced the risk of cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma.¹

Findings come from an updated analysis data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098). Any-grade CRS occurred in 25.0% of patients in the prophylactic tocilizumab cohort compared with 72.1% of those who received teclistamab without tocilizumab. Grade 1 and 2 CRS affected 8.3% and 16.7% of patients, respectively, in the prophylactic treatment arm; investigators reported no grade 3 events. The median time to CRS onset in this cohort was 2 days (range, 1-3), and events lasted for a median of 2 days (range, 2-4). Additionally, all instances of CRS were eventually resolved.

The median blood marrow plasma cell (BMPC) concentration was 8.0% (range, 0%-80%) in those without CRS, 19% (range, 8%-30%) in those with grade 1 CRS, and 62.5% (range, 30%-80%) in those with grade 2 events across the prophylactic treatment group. Additionally, most patients in each respective group had stage I disease per the International Staging System assessment (72.2% vs 50.0% vs 50.0%). Although no disease characteristic appeared to correlate with CRS in this cohort, investigators noted that a small sample size may preclude clinically meaningful conclusions.

Any-grade and grade 3/4 infections occurred in 79.2% and 25.0% of patients in the prophylactic treatment group, respectively. Other common any-grade and high-grade events in this group included neutropenia (62.5% vs 62.5%), anemia (58.3% vs 25.0%), and thrombocytopenia (50.0% vs 25.0%). Data showed 1 instance of grade 5 pulmonary embolism at 20 days following the final dose of teclistamab.

“With longer follow-up, there are no new safety signals or impact on response to teclistamab, and further data are needed to inform potential risk factors for higher-grade CRS,” lead study author Niels W.C.J van de Donk, MD, PhD, a professor in Hematology at the Amsterdam University Medical Center in Amsterdam, Netherlands, said in the presentation.¹ “Prophylactic tocilizumab may be considered to mitigate the risk of CRS for outpatient dosing of teclistamab.”

Findings from this presentation pertained to a cohort of 24 patients in the MajesTEC-1 trial after a median follow-up of 8.1 months after treatment with prophylactic tocilizumab. In this cohort, patients received teclistamab at 1.5 mg/kg every week or as a comparable fixed dose following a single dose of tocilizumab and step-up dosing. Patients received tocilizumab at 8 mg/kg intravenously within 4 hours of the initial teclistamab step-up dose.

Patients were also eligible to receive premedication with dexamethasone, acetaminophen (Tylenol), and diphenhydramine (Benadryl) during step-up dosing of teclistamab. Investigators hospitalized patients for 48 hours following each step-up dose and after the first study treatment dose.

The median patient age in the prophylactic tocilizumab cohort was 72 years. Additionally, most patients were male (58.3%), White (79.2%), and had an ECOG performance status of 0 (54.2%). Of note, 20.8% of patients had 1 or more extramedullary plasmacytomas, and 20.8% had BMPC concentrations of 60% or higher. Disease characteristics in this prophylactic treatment cohort were generally comparable with those reported among patients enrolled on the MajesTEC-1 trial overall.

Responses across the prophylactic treatment cohort appeared to be similar to those reported across the overall MajesTEC-1 trial population.² The objective response rate (ORR) was 72.7% with prophylactic tocilizumab vs 63.0% with teclistamab only. In each respective group, the complete response (CR) or better rate was 18.2% vs 46.1%, the very good partial response (VGPR) rate was 40.9% vs 13.3%, and the PR rate was 13.6% vs 3.6%. Investigators hypothesized that the relatively lower CR or better rate in the prophylactic treatment group may be attributable to a limited number of available bone marrow samples to confirm the CR and follow-up duration.

Interleukin-6 (IL-6) induction in the prophylactic treatment group was typically comparable with that in the general MajesTEC-1 population, although the magnitude of IL-6 induction was more pronounced in the prophylactic treatment group. Additionally, the duration of IL-6 signaling blockade lasted across the period of teclistamab step-up dosing.

REFERENCES:

1. van de Donk NWCJ, Garfall AL, Benboubker L, et al. Longer-term follow-up of patients (pts) receiving prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) in the phase 1/2 MajesTEC-1 study of teclistamab in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;42(suppl 16):7517. doi:10.1200/JCO.2024.42.16_suppl.7517

2. Garfall AL, Nooka AK, van de Donk NWCJ, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(suppl 16):7540. doi:10.1200/JCO.2024.42.16_suppl.7540