Talquetamab Versus Real-World Physician's Choice Treatment: Comparative Effectiveness in Patients With Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Background Talquetamab, a first-in-class GPRC5D×CD3 bispecific antibody, is approved for treatment of triple-class exposed (TCE) patients with relapsed/refractory multiple myeloma (RRMM) based on MonumenTAL-1 results. We evaluated the comparative effectiveness of talquetamab in MonumenTAL-1 versus real-world physician's choice (RW) treatment. Materials and Methods An external control arm for MonumenTAL-1 was created from eligible patients in the Flatiron Health database who satisfied key MonumenTAL-1 eligibility criteria (n = 629 with 1169 eligible lines of therapy). Patient-level data from MonumenTAL-1 were included for patients who received subcutaneous talquetamab 0.4 mg/kg QW (n = 143) and 0.8 mg/kg Q2W (n = 145). After adjusting for baseline covariate imbalances, comparative effectiveness was assessed for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). Results Baseline covariates were comparable across cohorts after adjustment. Talquetamab 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts, respectively, showed significant improvement in PFS (HR, 0.55 [95% CI, 0.44-0.69; P<0.0001; median, 7.5 vs. 4.0 months] and 0.40 [95% CI, 0.31-0.53; P<0.0001; median, 14.2 vs. 4.0 months]), TTNT (HR, 0.59 [95% CI, 0.47-0.74; P<0.0001; median, 9.1 vs. 5.1 months] and 0.45 [95% CI, 0.35-0.59; P<0.0001; median, 13.3 vs. 5.1 months]), and OS (HR, 0.56 [95% CI, 0.40-0.78; P=0.0007; median, NR vs. 16.5 months] and 0.48 [95% CI, 0.33-0.70; P=0.0002; median NR vs. 15.9 months]) versus RW treatment. Conclusion Both talquetamab schedules demonstrated superior effectiveness over RW treatment for all outcomes assessed. These data suggest talquetamab as an effective novel immunotherapy option in patients with TCE RRMM. Microabstract Talquetamab has been evaluated in the single-arm MonumenTAL-1 trial in patients with relapsed/refractory multiple myeloma. Effectiveness of talquetamab was assessed against outcomes of real-world treatments using indirect treatment comparison methodology. Talquetamab led to better outcomes compared to standard treatments, suggesting that novel immunotherapies such as talquetamab may be a superior treatment option versus previous standard regimens.