Infection risk associated with talquetamab in relapsed/refractory multiple myeloma: a systematic review with meta-analysis of talquetamab monotherapy and descriptive analysis of combination therapy.

Background: Talquetamab, a first-in-class G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, demonstrates substantial clinical activity in relapsed/refractory multiple myeloma (RRMM). However, immune dysfunction associated with advanced disease, extensive prior therapies, and bispecific antibody-mediated immune modulation may increase susceptibility to infections. This systematic review and meta-analysis aimed to characterize infection risk associated with talquetamab, with separate evaluation of monotherapy and combination therapy settings. Methods: PubMed, Embase, Web of Science Core Collection, and Cochrane Library databases were searched from inception to July 1, 2026. Studies reporting infection outcomes among RRMM patients treated with talquetamab-containing regimens were eligible. Outcomes included any-grade infections, grade ≥3 infections, infection-related mortality, reported pathogens, and preventive strategies when available. Because talquetamab monotherapy and combination regimens represent clinically distinct treatment strategies, quantitative analyses were restricted to monotherapy cohorts, whereas combination therapy studies were summarized descriptively. A random-effects model was used to estimate pooled infection incidence. Methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Series. Results: Six studies were included in the qualitative synthesis, including four talquetamab monotherapy cohorts and two talquetamab-based combination therapy cohorts. Quantitative meta-analysis included four monotherapy cohorts comprising 735 patients for any-grade infections and three cohorts comprising 584 patients for grade ≥3 infections. The pooled incidence of any-grade infections was 51% (95% CI, 34%-67%; I² = 94.2%), while the pooled incidence of grade ≥3 infections was 22% (95% CI, 17%-28%; I² = 59.6%). Given the limited number of available studies and substantial heterogeneity, these pooled estimates should be interpreted as exploratory and hypothesis-generating. Combination therapy cohorts, including talquetamab plus teclistamab and talquetamab-based regimens from MonumenTAL-3, demonstrated substantial infection burdens and were characterized descriptively rather than quantitatively. Infection-related mortality ranged from 0% to 3.2%. Frequently reported infections included viral infections (particularly SARS-CoV-2 and cytomegalovirus), bacterial pneumonia, and opportunistic infections such as Pneumocystis jirovecii pneumonia. Conclusions: Talquetamab monotherapy in heavily pretreated RRMM patients is associated with a clinically meaningful risk of infections, including severe infections. The substantial heterogeneity observed across studies likely reflects differences in patient characteristics, prior therapies, treatment settings, infection definitions, and supportive care strategies. Combination bispecific antibody regimens may represent a potentially higher infection burden requiring enhanced infection surveillance and preventive approaches. Further prospective studies are warranted to better define infection risk factors and optimal prevention and management strategies during talquetamab therapy. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261357352, identifier CRD420261357352.