P42 health-related quality of life in patients with relapsed/refractory multiple myeloma treated with talquetamab, a g protein-coupled receptor family c group 5 member d x cd3 bispecific antibody, from monumental-1

Introduction: Studies of patients (pts) with multiple myeloma (MM) indicate that those with more advanced and heavily pretreated disease have worse health-related quality of life (HRQoL) than those with early stage disease. In addition, treatment options are limited for triple-class exposed relapsed/refractory MM (RRMM), with less hope of improving HRQoL. Talquetamab (TAL), a first-in-class, off-the-shelf, T-cell redirecting bispecific antibody targeting both GPRC5D and CD3 receptors. Patient reported outcomes (PROs) data on HRQoL, symptoms, and functioning were collected in phase (ph) 2 cohorts of MonumenTAL-1, a ph 1/2 trial (NCT03399799/NCT04634552) of TAL in RRMM pts. Here we report PROs, focusing on global health status (GHS), physical functioning, pain, and fatigue, for 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort. Data for 0.8 mg/kg SC every other week (Q2W) cohort are immature. Methods: Enrolled pts in ph 2 had received ≥3 prior lines of therapy, including ≥1 proteosome inhibitor/≥1 immunomodulatory drug, and ≥1 anti-CD38 monoclonal antibody (triple-class exposed). Post screening, pts received TAL priming doses, requiring hospitalization, before Cycle (Cy)1. European Organization for Research and Treatment of Cancer Quality of Life Core 30 item (EORTC QLQ-C30) questionnaires was administered at screening, Cy1, and then every other cycle. It included a subscale to measure HRQoL, 5 functional scales, 3 symptom subscales, and 6 additional single items. Score range from 0-100; higher scores indicate better GHS and functioning, with higher scores indicating more symptom severity. PRO compliance was calculated as number of completed assessments divided by number of pts on study treatment at each assessment time point. Treatment effect was assessed with a mixed-effects model with repeated measures. For analysis of proportion of pts with meaningful improvement, threshold for meaningful improvement from baseline was change ≥10 points. Kaplan-Meier estimate was used to determine time to worsening. Results: For pts treated with 0.4 mg/kg SC QW (n=122) compliance for EORTC QLQ-C30 was 96% at screening and >80% at most post-treatment visits. After an immediate decline in overall HRQoL between screening and Cy1, pts had meaningful improvements in EORTC QLQ-C30 GHS and a meaningful reduction in pain symptoms (Figure). For fatigue symptoms, mean change for the 0.4 mg/kg cohort was -8 (95% CI -13.83, ‑2.26) at Cy9 and reached a mean decrease (ie improvement) of 10 points (95% CI -19.31, -0.93) at Cy13. Similar results were noted in physical (LS mean [LSM] change for 0.4 mg/kg at Cy9: 6.5 (95% CI 2.05, 10.93) and role (LSM change at Cy9: 11.4 (95% CI 4.55, 18.25) functioning subscales. With treatment, proportion of pts with meaningful improvement was high; for example, at Cy9 for the 0.4 mg/kg cohort, 42% improved in GHS, 34% physical functioning, 40% role functioning, 86% pain symptoms, and 78% in fatigue symptoms. Median time to worsening for the 0.4 mg/kg SC QW cohort ranged from 2 months (role and social functioning) to 9 months (nausea/vomiting). Overall, changes in PROs were similar in 0.8 mg/kg SC Q2W cohort; however, conclusions are limited due to short follow-up and small sample size. Conclusions: With TAL, pts reported improvement in overall HRQoL and physical and role functioning, and a decrease in pain and fatigue. These results are consistent with clinical benefits of TAL as observed for the efficacy results of MonumenTAL-1 study.