P-091: Talquetamab versus Belgian real-world clinical practice in triple-class exposed relapsed and refractory multiple myeloma patients using adjusted comparison.

Introduction: Triple-class exposed (TCE) patients (pts) with relapsed and refractory multiple myeloma (RRMM) face a challenging outlook with limited treatment options, mainly consisting of recently approved B-cell maturation antigen-targeting agents. Talquetamab, a bispecific antibody targeting GPRC5D and CD3, was granted an orphan drug designation and approved by EMA as of August 2023 as treatment for TCE RRMM pts based on the single-arm phase 1/2 MonumenTAL-1 trial. The effectiveness of talquetamab in this trial was compared against real-world clinical practice (RWCP), using individual patient data (IPD) from the retrospective Belgian patient cohort in BELCOMM (Belgium Comparator study in Multiple Myeloma)

Methods: The external control arm for MonumenTAL-1 was constituted from TCE RRMM pts in BELCOMM treated with therapies used in RWCP. They had ECOG score ≤2, ≥ 3 prior lines of therapy (LOTs), and ≥1 subsequent active MM therapy after becoming TCE. IPD were available for MonumenTAL-1 pts (cut-off date January 17^th, 2023) and RWCP pts in BELCOMM (data collection March 2017-May 2021).

Inverse probability weighting (IPW) and multivariable regression were used to balance confounding factors between both patient cohorts. The comparative effectiveness of talquetamab vs RWCP was assessed for overall response rate (ORR), very good partial response rate or better (≥VGPR), progression-free survival (PFS), time to next treatment (TTNT) and overall survival (OS) in the treated population. For ORR and ≥VGPR, weighted logistic regression was used to estimate an odds ratio (OR) and 95% confidence interval (CI). The ORs were also transformed to estimate response rate ratios (RR). For PFS, TTNT and OS, weighted Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% CIs.

Results: From MonumenTAL-1, 143 pts (143 LOTs) from the 0.4 mg/kg weekly cohort and 145 pts (145 LOTs) from the 0.8 mg/kg Q2W cohort and from BELCOMM 123 pts (268 LOTs) were included in the all-treated analyses. Comparisons of both the 0.4 mg/kg as well as the 0.8 mg/kg cohorts with the RWCP cohort demonstrated statistically significant results in favour of talquetamab with respect to all endpoints. For ORR, the RR [95% CI] for talquetamab vs RWCP were 2.51 [1.88, 3.36] with 0.4 mg/kg dosing and 2.34 [1.75, 3.13] with 0.8 mg/kg dosing. While for ≥VGPR these were 5.32 [3.51, 8.07] and 5.42 [3.58, 8.20], respectively. The HR [95% CI] for talquetamab vs RWPC were 0.47 [0.36, 0.61] and 0.35 [0.26, 0.47] for PFS, 0.42 [0.32, 0.54] and 0.34 [0.25, 0.45] for TTNT, and 0.34 [0.24, 0.49] and 0.32 [0.21, 0.47] for OS, respectively.

Conclusions: Both talquetamab 0.4 mg/kg weekly and 0.8 mg/kg Q2W showed superior effectiveness compared to RWCP treatments administered for each measure of clinical effectiveness in Belgian TCE RRMM pts and indicate its potential as a novel and effective treatment in TCE RRMM pts.