Introduction Teclistamab (Tec) is a bispecific antibody targeting BCMA and CD3 for the treatment of triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) is a common adverse event (AE) almost exclusively occurring during step-up dosing (SUD). To mitigate potential life-threatening CRS, patients are hospitalized or closely monitored for 48 hours after each SUD, which imposes a significant burden for the healthcare system. Tocilizumab (Toci) is an IL-6 receptor antibody approved for the treatment of CRS, based on severity. Toci may be used as CRS prophylaxis, but this practice remains largely investigational.

In Denmark, where access to healthcare services is universal and publicly financed, Tec has been reimbursed for the treatment of TCE RRMM since February 2024. Local standards in prophylactic strategies during SUD however differ between centers. Since May 2024, patients at the University Hospital of Copenhagen have received one dose of prophylactic Toci (“PToci”) prior to the first Tec SUD, while other departments have not implemented this practice. This provides a real-world opportunity to investigate the safety and efficacy of PToci during Tec SUD, focusing on CRS rates, treatment-emergent AEs and efficacy outcomes in an otherwise unselected nationwide population.

Methods In this retrospective, multicenter study, myeloma specialists from all Danish healthcare regions reviewed patient charts of all TCE RRMM patients who received standard-of-care Tec since its reimbursement in February 2024 until the data cut-off in May 2025. Collected data included baseline demographics, prior lines of therapy (pLOT), response rates, progression-free survival (PFS), duration of response (DOR), overall survival (OS), AEs, and clinical use patterns including prophylactic strategies. The study was conducted in collaboration with Johnson & Johnson and financially supported by GSK.

Results A total of 94 patients received Tec; 47 patients received PToci and 47 did not (“NoToci”). All patients were hospitalized during SUD. Median follow-up was 6 months (IQR 3-8) for PToci and 9 months (IQR 6-13) for NoToci.

The median age at Tec initiation was 71 years in both groups and both groups had a median of 4 pLOTs and a median of 6 years since diagnosis. The gender distribution was 49% males (PToci) vs. 53% males (NoToci). Performance status was 0-1 in 92% (PToci) vs. 94% (NoToci).

Prior exposure: 98% were TCE in both groups; 73% had undergone prior transplant in both groups; triple-class refractoriness was present in 83% (PToci) vs. 77% (NoToci).

High-risk FISH defined as t(4;14), t(14;16), or del17p was present in 28% (PToci) vs. 38% (NoToci); measurable disease at Tec initiation was present in 87% (PToci) vs. 79% (NoToci).

CRS occurred in 8% of patients (PToci) vs. 66% (NoToci) (p=0.001).

In the PToci group, 6% of patients had grade 1 CRS and 2% had grade 2 CRS. In the NoToci group, 36% of patients had grade 1 CRS and 30% grade 2 CRS. All episodes of CRS occurred during SUD, and no grade ≥ 3 CRS events were observed in either group.

Infections of any grade occurred in 68% of patients in the PToci group vs. 53% of the NoToci group (p=0.139). Grade ≥ 3 infections occurred in 21% of the PToci group vs. 27% of the NoToci group (p=0.472).

In the PToci group, overall response rate (ORR) was 64% with a very good partial response (VGPR) or better rate of 60%; estimated median PFS was 12.5 months; median DOR was not reached, estimated 12-month DOR was 66%; median OS was not reached, and estimated 12-month OS was 67%.

In the NoToci group, ORR was 55% and VGPR or better rate was 49%; estimated median PFS was 12.1 months; median DOR was not reached, estimated 12-month DOR was 90%; median OS was not reached, and estimated 12-month OS was 71%.

The differences in PFS, DOR and OS were not statistically significant.

Conclusion: In this multicenter, nationwide, real-world study, prophylactic administration of tocilizumab prior to step-up dosing of Tec was associated with significantly lower incidence of CRS without increased infection rates or impaired efficacy outcomes. Our findings support the feasibility of incorporating prophylactic tocilizumab into future Tec step-up regimens as enhanced safety may support broader use of out-patient step-up dosing. Our observations are limited by the retrospective and non-randomized nature of the study. Prospective validation of prophylactic strategies is warranted.

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2025
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