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

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.

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.

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).

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.