Abstract Introduction: Talquetamab (Tal) is the first bispecific antibody (BsAb) that targets the G protein-coupled receptor family C group 5 member D approved by the FDA and EMA. It is intended for patients with relapsed refractory multiple myeloma (RRMM) who have previously received treatment with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Findings from the MonumenTAL-1 study indicate that Tal offers a new, effective, and manageable treatment option for this challenging patient group. Gathering real-world data is essential to assess its effectiveness and safety outside the rigorously defined clinical trial environments, helping to inform future enhancements in the clinical application of these therapies. Here, we present data from a programmed interim analysis further supporting the effectiveness and safety of Tal in triple-class exposed (TCE) RRMM patients outside of clinical trials. Methods: BiTAL is an ongoing, retrospective, noninterventional study that aims to describe the management and outcomes of patients treated with Tal in TCE RRMM patients outside of clinical trials, involving 68 sites across Spain. Informed consent was obtained for all patients. Data were collected from patient medical records, including demographics, disease characteristics, prior therapies, effectiveness, and safety. Treatment outcomes were assessed based on response rates, progression free survival (PFS), and overall survival (OS). Responses were evaluated according to International Myeloma Working Group criteria. Results: At data cut-off (May 12th 2025), 163 eligible patients who started Tal treatment on/before August 24th, 2024, from 68 sites were included. All received Tal as part of a pre-approval access program. Most patients, 87.8% (129/147), received Tal biweekly (Q2W), the rest weekly, following SmPC. Median age was 66 years in this heavily pre-treated population, with a median of 4 prior lines of therapy. Charlson index ≥2: 39/147 (27%), frail (Facon T et al. Leukemia 2020): 48/129 (37.2%), not eligible for MonumenTAL-1: 48.4% (60/124). All were triple-class exposed and most penta-class exposed (103/152, 67.8%). Thirty-five-point five percent (54/152) had prior anti-BCMA treatments (CAR T: 3.7%, BsAb: 3.7%, ADCs: 25.8%). Seventy-three percent and 28.8% were triple- and penta-class refractory, respectively. With median follow-up of 10.9 (0.1–26.2) months overall, 12.2 months (0.1–26.2) for Q2W group, overall response rate (ORR) was 83.8% (109/130) and 84.5% (100/118), with ≥VGPR in 65.4% (85/130) and 66.1% (78/118), respectively. Median PFS was 8.6 (6.5–10.7) and 9.9 (7.6–12.1) months; median OS: 26.2 (15.6–36.7) and 26.2 (17.4–34.9) months for overall and Q2W groups. In patients completing step-up and first maintenance dose and achieving ≥PR (102/126 and 93/113), median PFS: 11.4 (7.6–15.1) and 11.4 (6.1–16.7) months; median OS: 26.2 (20–32.4) months for both groups. Median treatment duration: 7.8 (0.1–24) and 8.2 (0.1-24) months, overall and Q2W, respectively. TEAEs of interest for the overall population: skin (all: 75.5%, G≥3: 2.5%), CRS (all: 55.2%, G≥3: 13.5%), infections (all: 47.3%, G3–4: 8.6%), dysgeusia (47.9%), nail (44.8%), weight-loss (10.4%, G≥3: 1.2%), ICANS (8%, G≥3: 1.8%). Five patients (3%, 5/163) discontinued due to TEAEs (all Q2W); five (3%) had Tal dose reductions to manage TEAEs. Fifty-nine-point nine percent were alive; disease progression was the most frequent cause of death (30.7%, 50/163; 31.8%, 41/129), TEAEs: 3.7% (6/163) and 4.7% (6/129), for overall and Q2W respectively. No new safety signals identified.Conclusion: The BiTAL study shows remarkable performance of Tal in a challenging RRMM population. Despite being a difficult to manage population, high ORR and survival underscore its effectiveness. Notably, most patients completed first maintenance and achieved ≥PR, showing even better outcomes. The safety profile was favorable and consistent with previous findings. While the retrospective nature of this study imposes some limitations, this close to real-world data reflects the drug's performance outside clinical trials, supporting its integration into routine clinical practice.
Arnao et al. (2025) studied this question.