Teclistamab Maintains Activity in Heavily Pretreated Real-World Myeloma

Real-world outcomes from the multinational REALiTEC study (NCT06285318) suggest that teclistamab (Tecvayli) retains clinically meaningful activity and a manageable safety profile in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) treated outside the clinical trial setting, according to findings published in Haematologica.¹

The retrospective observational analysis reported an overall response rate (ORR) of 60.2% and a median progression-free survival (PFS) of 9.7 months among patients receiving the B-cell maturation antigen (BCMA)-targeted bispecific antibody, outcomes broadly consistent with those reported in the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098) that supported the drug’s regulatory approval.²

The findings provide evidence that teclistamab effectiveness in routine practice may approximate outcomes observed in clinical trials, despite a population with extensive prior therapy and high-risk disease features. Investigators noted that the cohort included patients often excluded from prospective trials, highlighting the potential value of real-world evidence in guiding treatment decisions in advanced myeloma.

Study Overview

REALiTEC was a retrospective, multicountry observational study evaluating teclistamab use in routine clinical practice across 8 countries in Europe and Israel. The analysis included 113 adults with RRMM treated at 23 centers who received at least 1 dose of teclistamab outside a clinical trial prior to December 31, 2022.¹

Most patients (88.5%) accessed the therapy through pre-approval access programs. The population reflected a heavily pretreated group typical of late-line myeloma management: the median age was 66 years, and patients had received a median of 6 prior lines of therapy. Notably, 78.8% were triple-class refractory, having received proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, and 44.2% were penta-class refractory. Approximately 35% had previously received a BCMA-directed therapy.

At a median follow-up of 20.7 months, the ORR was 60.2%, with 52.2% of patients achieving a very good partial response (VGPR) or better. Median duration of response (DOR) was 20.3 months. Median PFS was 9.7 months, and median overall survival (OS) reached 26.3 months.

Investigators observed that deeper responses correlated with improved outcomes. Among patients achieving at least a VGPR, the median DOR extended to 26.1 months, and 12-month PFS and OS rates were 71.2% and 83.1%, respectively.

Safety Findings

The safety profile of teclistamab in this real-world cohort was consistent with prior clinical studies. The most commonly reported adverse events included infections in 70.8%, cytokine release syndrome (CRS) in 55.8%, neutropenia in 35.4%, and anemia in 25.7%.

Nearly all CRS events were low grade and 94.4% occurred during step-up dosing or the first maintenance dose. The most common intervention for CRS was antipyretics, with tocilizumab (Actemra) being used in 15% and corticosteroids in 9.7%; no prophylactic tocilizumab was used in the cohort. Immune effector cell–associated neurotoxicity syndrome events were rare and generally mild.

Investigators reported that infections remained a major complication, including grade 3 or 4 events in a substantial proportion of patients (38.9%) and grade 5 events in 5.3%. Over 60% received immunoglobulin G replacement therapy with a majority receiving it prophylactically. Treatment discontinuation occurred in 17.7% of patients, including cases related to infections. The authors noted that lower rates of serious infection and hematologic toxicities in real-world data compared with the clinical trial rates reflect that there is greater awareness and proactive supportive care for these adverse events.

Clinical Context

In MajesTEC-1, teclistamab demonstrated an ORR of approximately 63% in heavily pretreated patients, with durable responses and a manageable toxicity profile, albeit with a 55% grade 3 or 4 infection rate and a significant number of deaths, primarily attributed to COVID-19.² Real-world studies such as REALiTEC aim to determine whether similar outcomes can be achieved outside the controlled environment of clinical trials.

Investigators cautioned that comparisons with prospective trials should be interpreted carefully as it was retrospective and lacked a comparator arm, which limits the ability to assess relative treatment benefit.¹ Differences in patient selection, supportive care practices, and response assessment may also influence outcomes. Some clinical data such as minimal residual disease status and detailed cytogenetic information were incomplete, restricting the ability to perform more granular subgroup analyses on the full population.

Nevertheless, the study provides one of the longest real-world follow-ups reported to date for teclistamab and includes a diverse patient population treated in routine practice settings. The investigators suggested that future analyses, including follow-up cohorts and prospective real-world registries, may help clarify optimal sequencing strategies for BCMA-directed therapies and identify factors influencing long-term outcomes.

REFERENCES

1. Uttervall K, Kortüm KM, Perrot A, et al. REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials. Haematologica. Published online March 5, 2026. https://doi.org/10.3324/haematol.2025.289281

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 relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(Suppl 16). doi: 10.1200/JCO.2024.42.16_suppl.7540