Real-world outcomes of talquetamab in Relapsed/Refractory multiple myeloma

Abstract Background: Talquetamab (Talq), a GPRC5D-targeted bispecific antibody (BsAb), has demonstrated efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). However, real-world evidence remains limited. We conducted a single center retrospective study to evaluate the outcomes and prognostic factors in RRMM patients (pts) treated with Talq. Methods: We analyzed 87 RRMM pts treated with Talq at Moffitt Cancer Center from 9/2023 to 06/2025. Responses were assessed by IMWG criteria; toxicities per ASTCT consensus, measurable residual disease (MRD) by next-generation sequencing (per 106 cells). Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan-Meier methods and Cox regression. Logistic regression identified factors associated with overall response rate (ORR; ≥PR). Patients receiving Talq as bridging therapy for CAR-T were censored for PFS analysis at the time of CART. Results Of 87 pts, 53% were female, 14% were Black, and 16% were Hispanic. Median age was 67 (range 39–90) years. Most (93%) received treatment in the inpatient setting; all outpatient treatment was given with tocilizumab prophylaxis. Median prior lines of therapy was 6 (range 2–11); 87% were triple-refractory, and 45% penta-refractory. Talq was used as bridging to CAR-T in 36% pts. Prior therapies included autologous stem cell transplant (ASCT) in 57 (66%), CAR-T in 46 (53%), and prior BsAb in 29 (33%). High-risk cytogenetics were present in 64 (74%), and 24 (28%) had high (> 50%) marrow plasma cell burden. Twenty-nine percent pts had ECOG performance status (PS) of ≥2. Best overall responses were: sCR in 15 (17%), CR in 15 (17%), VGPR in 14 (16%), PR in 25 (29%), MR in 1 (1%), SD in 2 (2%), and PD in 12 (14%). ORR was 79%, with 72% achieving response by day 30. Seventy percent (29/41) pts attained MRD negativity by NGS. Median progression-free survival (PFS) was 8.4 months (95% CI 3.9–12.6), median overall survival (OS) was not reached, with a median follow-up of 10.1 months (range 0.7–22.7). The median duration of Talq treatment was 2.5 months (range 0–18.7). In univariate analysis, high-risk cytogenetics were associated with inferior PFS (HR 2.64, 95% CI: 1.10–6.29; p = 0.023). Inferior OS was observed in patients with high-risk cytogenetics (HR 9.70, 95% CI: 1.31–71.62; p = 0.006) and those with prior BsAb exposure (HR 2.36, 95% CI: 1.00–5.62; p = 0.044). In multivariate analysis, PFS remained significantly worse in patients with prior BsAb exposure (HR 2.35, 95% CI: 1.11–4.97; p = 0.026) and those with high-risk cytogenetics (HR 3.21, 95% CI: 1.20–8.57; p = 0.020). Prior BsAb exposure was also associated with inferior OS (HR 2.91, 95% CI: 1.21–6.98; p = 0.017). No significant differences in outcomes were noted based on gender, prior ASCT, CAR-T therapy, prior BCMA-targeted therapies, PS, or marrow disease burden. ORR was significantly lower among pts with prior BsAb (67% [18/27] vs 89% [39/44]; OR 0.26, 95% CI 0.08–0.88, p=0.03), and those with high-risk cytogenetics (76% [47/62] vs 100% [22/22], p=0.009). No ORR differences were observed based on gender, prior ASCT, CAR-T, BCMA exposure, PS, or marrow burden. Cytokine release syndrome (CRS) occurred in 50 pts (57%), with ≥Grade 2 events in 20 (23%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 15 (17%), with ≥Grade 2 events in 8 (9%). None of the patients treated in the outpatient setting experienced Grade ≥2 CRS/ICANS, suggesting effective mitigation with prophylactic tocilizumab. Other toxicities include oral toxicities (dysgeusia, dry mouth, dysphagia, mucositis, and oral sores) in 64 pts (73.6%), skin toxicities such as rash, dry skin, and desquamation in 57 pts (65.5%), and nail toxicities, including pitting, onycholysis, and brittle nails, were reported in 30 pts (34.5%). Infections occurred in 29 (33%) pts: bacterial (n=12), viral (n=13), bacterial + viral (n=2), and fungal (n=2); 14 of them required IV antibiotics/hospitalization. Talq was discontinued in 55 (63%)—due to bridging to CAR-T (n=21), progression (n=22), toxicity (n=8), or death (n=4). Conclusions In this real-world RRMM cohort, Talq demonstrated an ORR of 79%, with early responses and manageable toxicity. Prior BsAb exposure, and high-risk cytogenetics were independently associated with inferior outcomes. These findings underscore the need for risk-adapted strategies and treatment continuity to optimize BsAb therapy in advanced myeloma.