Teclistamab 30mg/3ml solution for injection vials

Extramedullary disease (EMD) in multiple myeloma refers to soft-tissue plasmacytomas that spread hematogenously and grow independently of bone, an aggressive phenotype that has been associated with poorer responses and shorter survival across successive treatment eras. Bispecific antibodies are highly active in relapsed or refractory multiple myeloma (RRMM), but their efficacy in patients with baseline EMD has not been quantitatively synthesized. We performed a systematic review and meta-analysis, reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance, of prospective trials of B-cell maturation antigen (BCMA)- or G protein-coupled receptor class C group 5 member D (GPRC5D)-directed CD3 bispecific antibodies in RRMM that reported the objective response rate (ORR) in patients with baseline EMD. One estimate per trial was included; proportions were pooled using a random-effects model on the logit scale with restricted maximum-likelihood estimation of between-study variance, and heterogeneity was assessed with the Cochran Q test and the I-squared statistic; fixed-effect and leave-one-out sensitivity analyses were performed, and risk of bias was appraised for each EMD subgroup. Four prospective studies comprising 144 patients with baseline EMD were included. Study-level ORRs were 58.3% for teclistamab, 38.5% for elranatamab, 52.6% for linvoseltamab, and 44.6% for talquetamab when recommended phase 2 dose cohorts were combined. The random-effects pooled ORR was 45.2% (95% CI, 37.2-53.4), with no observed between-study heterogeneity (I-squared = 0%); estimates were identical under a fixed-effect model, and leave-one-out pooled ORRs ranged narrowly from 44.0% to 47.6%. BCMA- and GPRC5D-directed bispecific antibodies produce objective responses in approximately half of patients with RRMM and baseline EMD, with broadly similar activity across agents despite high-risk biology, although the small number of trials and their differing, sometimes paramedullary-inclusive, definitions of EMD warrant caution in interpreting this estimate. These pooled estimates provide a benchmark for patient counseling and trial design and support combination strategies to improve outcomes in this population.

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BackgroundTeclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody (BsAb), has shown remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). However, its mechanism leads to profound hypogammaglobulinemia, making infection a critical concern. This systematic review and meta-analysis aimed to quantify the infectious burden and contrast outcomes between clinical trial and real-world evidence (RWE).MethodsWe systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for studies reporting infection outcomes in RRMM patients treated with teclistamab. Pooled incidences of any-grade and grade ≥3 infections were calculated using a random-effects model. Subgroup analysis compared the pivotal MajesTEC-1 trial with multi-institutional RWE cohorts.ResultsFive studies encompassing 714 patients were included. The overall pooled incidence was 56.5% (95% CI: 43.1%-69.9%) for any-grade infections and 27.6% (95% CI: 21.0%-34.3%) for grade ≥3 infections. Subgroup analysis revealed a significantly higher risk in the clinical trial compared to RWE (Any-grade: 76.4% vs. 45.4%, pConclusionsTeclistamab is associated with a substantial and cumulative infectious burden. The lower infection rates in RWE may reflect shorter follow-up and evolving prophylactic strategies. Standardized infection surveillance, including regular IgG monitoring and consideration of IVIG replacement in patients with low IgG levels, may help optimize the safety of BCMA-directed bispecific therapies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261297645.

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Abstract Background: Bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab) and GPRC5D (talquetamab) have transformed relapsed/refractory multiple myeloma (RRMM), achieving overall response rates (ORR) of 61–70% in heavily pretreated patients. However, standard weekly dosing is associated with grade ≥3 infections in 45–55% of recipients, driven by prolonged hypogammaglobulinemia and T‑cell exhaustion. Emerging evidence suggests that reducing dosing frequency to every 2 or 4 weeks after deep response may preserve efficacy while curbing infectious toxicity. Objective: To systematically evaluate whether reduced‑frequency dosing (Q2W or Q4W) of FDA‑approved BsAbs in RRMM maintains clinical efficacy compared with standard weekly dosing, and to quantify the associated reduction in infection‑related adverse events. Methods: A PRISMA‑guided systematic review was conducted. PubMed, Embase, Scopus, Cochrane CENTRAL, Web of Science, and major hematology conference proceedings (ASH, ASCO, EHA, SOHO; 2022–2026) were searched. Included were prospective trials, cohort studies, and post hoc analyses reporting reduced-frequency BSAb dosing in adults with RRMM. Primary efficacy outcomes were ORR, progression‑free survival (PFS), and response maintenance after dose reduction. Secondary outcomes were grade ≥3 infections, hypogammaglobulinemia, and treatment discontinuation. Risk of bias was assessed using the ROBINS-I and the Newcastle-Ottawa Scale. Narrative synthesis was performed due to heterogeneity. Results: Fourteen studies (three pivotal trials with de‑escalation cohorts, six real‑world studies, five sub‑analyses) comprising >1,200 patients were included. For teclistamab, transition from weekly to Q2W after ≥6 months of complete response (CR) preserved responses in 100% (37/37) of patients (MajesTEC‑1). Real-world data showed comparable median PFS between the weekly and reduced-frequency groups (9.1 vs 11.3 months; p=0.141), despite lower dose intensity. All-grade infections declined from 6.08 to 2.25 per patient-year with Q2W dosing. For elranatamab, Q4W maintenance after ≥6 cycles of Q2W maintained responses in 92.6% (25/27) of patients at 6 months, with grade 3–4 infections decreasing from 17.9% to 10.7% after Q4W transition (Pfizer, 2025). For talquetamab, the FDA-approved Q2W primary schedule (0.8 mg/kg) achieved an ORR of 71% and a median PFS of 11.2 months, with grade ≥3 infections at 21%, substantially lower than those observed with BCMA-targeted agents (Chari et al., 2025). Across all agents, no study reported loss of response attributable to dose de‑escalation, but selection bias limits causal inference. Conclusion: Reduced‑frequency dosing (Q2W or Q4W) of teclistamab, elranatamab, and talquetamab in RRMM patients who have achieved deep, sustained responses preserves efficacy while substantially lowering infection rates. These findings support regulatory approvals for biweekly and monthly maintenance schedules. However, the evidence remains derived from non-randomized, single-arm cohorts with a moderate risk of bias. Prospective randomized trials are urgently needed to define optimal de-escalation timing, patient selection biomarkers, and comparative value against fixed-duration CAR T therapy.

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Background Multiple myeloma (MM) is a hematological malignancy with limited treatment options for patients with relapsed/refractory MM (RRMM). Teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, has shown promising results in clinical trials and real-world studies. Methods PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, ClinicalTrials.gov, and meeting libraries were searched from inception to 14 November 2024. The assessed outcomes included overall survival (OS), progression-free survival, time to next treatment, duration of response, overall response rate (ORR), ≥complete response (≥CR), ≥very good partial response (≥VGPR), VGPR, partial response, and adverse events. Results In total, 34 studies involving 4,064 patients were included. In pairwise meta-analysis, teclistamab demonstrated superior OS [hazard ratio (HR) = 0.69, 95% confidence interval (CI): 0.54–0.89; p = 0.037] compared to existing RRMM treatments. Real-world studies showed comparable ORR (62%, 95% CI: 58%–66%) but slightly lower survival outcomes, possibly because of shorter follow-up times and higher-risk populations. Subgroup analyses revealed enhanced efficacy with combination therapies (ORR: 85% vs 62%, p < 0.0001) and notable clinical benefits in the China cohort (≥VGPR: 77%, ≥CR: 58%). Safety profiles indicated manageable cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, though infection risks required vigilant management. Conclusions Teclistamab continues to be a promising and effective treatment option for RRMM patients, including those previously exposed to BCMA-targeted therapies, and offers new hope for overcoming resistance and achieving better early disease control. Further research is needed to optimize its application in diverse populations, particularly in Asian cohorts. Systematic Review Registration https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42025633838.

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