Comparative Efficacy of Talquetamab vs. Real-World Physician's Choice of Treatment in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: Updated Analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent.

内容摘要

Talquetamab, a bispecific antibody targeting GPRC5D, is approved for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) based on results from MonumenTAL-1. We report updated indirect comparisons of talquetamab vs. real-world physician's choice of treatment (RWPC) in patients with TCE RRMM. External control arms were created for three MonumenTAL-1 cohorts, two without prior T&#xa0;cell redirection (TCR) therapies who received subcutaneously administered talquetamab 0.4&#xa0;mg/kg weekly (QW; n&#x2009;=&#x2009;143) or 0.8&#xa0;mg/kg every other week (Q2W; n&#x2009;=&#x2009;154) and one with prior B&#xa0;cell maturation antigen (BCMA) TCR (n&#x2009;=&#x2009;75) who received either schedule (median follow-up [mFU] 38.2, 31.2, and 30.3&#xa0;months, respectively), from two real-world studies, LocoMMotion (mFU 26.4&#xa0;months) and MoMMent (mFU 27.1&#xa0;months). Imbalances in baseline covariates were adjusted using inverse probability weighting and multivariable regression. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), &#x2265;&#x2009;very good partial response (VGPR) rate, and &#x2265;&#x2009;complete response (CR) rate; odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional-hazards model. In the TCR-na&#xef;ve cohort, talquetamab Q2W had significantly improved outcomes vs. RWPC; RRs were ORR, 2.58;&#x2009;&#x2265;&#x2009;VGPR, 5.01;&#x2009;&#x2265;&#x2009;CR, 52.22 and HRs were DOR, 0.52 (p&#x2009;=&#x2009;0.0011); PFS, 0.47; TTNT, 0.46; OS, 0.35 (all p&#x2009;<&#x2009;0.0001). Results were similar in the QW cohort. The prior TCR cohort had favorable outcomes with talquetamab vs. RWPC; RRs were ORR, 3.03;&#x2009;&#x2265;&#x2009;VGPR, 4.88 and HRs were DOR, 0.09, (p&#x2009;=&#x2009;0.0004); PFS, 0.30 (p&#x2009;<&#x2009;0.0001); TTNT, 0.26 (p&#x2009;<&#x2009;0.0001) and OS, 0.37 (p&#x2009;=&#x2009;0.0020). With longer follow-up, these comparative analyses further demonstrate the clinical benefit of talquetamab over RWPC in patients with TCE RRMM, irrespective of prior TCR therapy. MonumenTAL&#x2011;1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584.