Assessment of health-related quality of life (HRQoL) in triple-class–exposed patients with relapsed or refractory multiple myeloma (RRMM) treated with linvoseltamab in the LINKER-MM1 trial.
Authors: Hoffman James E. , Bumma Naresh , Richter Joshua Ryan , Dhodapkar Madhav V. , Lee Hans C. , Suvannasankha Attaya , Zonder Jeffrey A. , Maly Joseph J. , Shah Mansi R. , Baz Rachid C. , DeVeaux Michelle , Ivanescu Cristina , Rodriguez-Lorenc Karen , Kroog Glenn Scott , Houvras Yariv J. , Inocencio Timothy J , Chi Lei , Harnett James , Ma Qiufei , Jagannath Sundar 
Published: June 2024

e23185

Background: Linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, is being evaluated in LINKER-MM1, a Phase 1/2 study in patients with RRMM (NCT03761108). Early results over 36 weeks of treatment showed promising efficacy and a generally manageable safety profile (Jagannath et al., ASH 2023), and improvement or stability in patient-reported outcomes (PROs) including pain and fatigue (Hoffman et al., ASH 2023). We now report PRO data over a treatment period of 76 weeks. Methods: We evaluated patients in LINKER-MM1 who received the 5-25-200 mg dosing regimen in Phases 1 and 2 (n = 117). Patients ≥18 years old with triple-class exposed RRMM were administered linvoseltamab at Weeks 1 (5 mg), 2 (25 mg), and 3 (200 mg), followed by 200 mg once weekly through Weeks 14 (Phase 2) or 16 (Phase 1), then every 2 weeks until progression. Patients with a very good partial response by Week 24 in Phase 2 transitioned to dosing every 4 weeks. The EORTC QLQ-C30 was administered at baseline, Week 4, and then every 4 weeks. Least squares (LS) mean change from baseline and 95% confidence interval (CI) were estimated at each timepoint and overall on all scales using a mixed effects model for repeated measures. A 10-point change from baseline was considered clinically meaningful. Results were stratified by objective response status (at least partial response). No adjustment for multiplicity was performed; statistical significance is nominal, with LS mean change from baseline considered statistically significant if 95% CI did not cross 0. Results: PRO completion rates were generally ≥80% through Week 44 and dropped slightly after Week 44. LS mean change showed improvement in Global Health Status/QoL at Week 12, reaching the clinically meaningful threshold at Week 44; clinically meaningful improvements were observed on role and social functioning scales at Weeks 24 and 28, respectively. Pain and fatigue significantly improved and reached the clinically meaningful threshold at Weeks 20 and 44, respectively; the clinically meaningful improvement in pain was generally maintained through Week 76. Overall LS mean change in pain was clinically meaningful (-10.2; 95% CI -13.7, -6.7). Among treatment responders, statistically significant improvements were observed on all scales, including clinically meaningful improvement in pain (-11.2; 95% CI -14.7, -7.6). Non-responders had statistically significant worsening in fatigue (9.9; 95% CI 0.8, 19.1); overall change from baseline was not significant on other scales. Conclusions: Over 76 weeks of treatment, improvements in measures of HRQoL including pain and fatigue were reported in patients with triple-class exposed RRMM receiving linvoseltamab; responders showed significant improvements on all scales. These PRO results support a favorable benefit–risk profile of linvoseltamab. Clinical trial information: NCT03761108 .