Linvoseltamab-gcpt (Lynozyfic) elicited nominal statistically significant improvements across patient-reported measures of function, symptoms, and overall health status in patients with relapsed/refractory multiple myeloma, according to health-related quality-of-life (HRQOL) findings from the phase 1/2 LINKER-MM1 trial (NCT03761108) published in Blood Neoplasia.1
Across all study assessments in the 117 patients treated at the full 200-mg dose, mixed-model least squares (LS) mean changes from baseline on the EORTC QOL Questionnaire Core 30 (QLQ-C30) showed improvement in global health status/quality of life (GHS/QoL; 7.0; 95% CI, 5.4-8.6), fatigue (−7.4; 95% CI, −10.0 to −4.9), and pain (−10.2; 95% CI, −13.8 to −6.6), with the pain improvement and a 10.4-point gain in social functioning (95% CI, 7.1-13.8) meeting the prespecified 10-point threshold for clinical meaningfulness. On the myeloma-specific 20-item module (QLQ-MY20), the future perspective scale improved by a clinically meaningful 11.9 points (95% CI, 9.9-13.9), and the EuroQol 5-dimension, 3-level visual analog scale (EQ-5D-3L VAS) improved by 8.0 points (95% CI, 5.0-11.0). No scale showed statistically significant or clinically meaningful worsening.
The patient-reported results paralleled the clinical activity previously observed with the human B-cell maturation antigen (BCMA)×CD3 bispecific antibody.
LINKER-MM1 is an ongoing open-label, multicenter phase 1/2 dose-escalation and dose-expansion trial evaluating linvoseltamab in adults with relapsed/refractory multiple myeloma. Eligible patients had received at least 3 previous lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody, or had triple-class–exposed, multi-refractory disease. Linvoseltamab was administered intravenously with step-up dosing at weeks 1 (5 mg), 2 (25 mg), and 3 (200 mg), followed by once-weekly 200-mg dosing through week 14 or 16 and then every-2-week dosing until progression or discontinuation; phase 2 responders meeting protocol criteria could transition to every-4-week administration.
HRQOL, a prespecified secondary end point, was assessed at baseline, week 4, and every 4 weeks thereafter using the QLQ-C30, QLQ-MY20, and EQ-5D-3L instruments, with changes estimated using mixed models for repeated measures. Because no adjustment for multiplicity was performed, all reported statistical significance is nominal. The analysis reflected the July 23, 2024, data cutoff, at which the 200-mg cohort had a median follow-up of 21.3 months.
Among the 117 patients, the median age was 70 years, 54.7% were male, and 70.9% were White. Overall, 82.1% had triple-class refractory disease, 76.9% were penta-exposed, and 39.3% had high-risk cytogenetics, and patients had received a median of 5 previous lines of therapy. At baseline, patients reported greater pain and a higher disease-symptom and treatment–side-effect burden than reference populations, along with a mean EQ-5D-3L VAS score of 60.9 that fell below general-population norms, reflecting impaired baseline HRQoL.
Improvements from baseline of nominal statistical significance were observed on all QLQ-C30 scales overall, with the largest functional gain in social functioning and the largest symptom improvement in pain. GHS/QoL reached nominal statistical significance as early as week 12, and physical and role functioning did so by week 20; improvements in fatigue and pain seen at week 16 were maintained at most subsequent assessments, with pain reaching the clinically meaningful threshold at week 20 and generally maintained through week 104. Improvements on all QLQ-MY20 scales and the EQ-5D-3L VAS were also of nominal statistical significance overall, and the future perspective scale reached the clinically meaningful threshold at most assessments starting at week 20.
Across the week 12, 24, 52, and 104 assessments, 70% to 94% of patients reported clinically meaningful improvement or maintenance on the QLQ-C30 scales, including clinically meaningful improvement in pain for 33% to 58% and in fatigue for 42% to 67%. Median time to definitive deterioration was not reached over 104 weeks on the QLQ-C30 GHS/QoL scale or any other PRO scale except the QLQ-MY20 future perspective scale and the EQ-5D-3L VAS (both 37.8 months), although few patients remained on study beyond 24 months.
Investigators stratified the analysis by objective response, defined as a best overall response of at least partial response per International Myeloma Working Group criteria. Among the 83 responders (70.9%), overall changes from baseline improved with nominal statistical significance on all scales, reaching the clinically meaningful threshold on the QLQ-C30 social functioning (LS mean change, 10.9; 95% CI, 7.6-14.3) and pain (−11.6; 95% CI, −15.3 to −7.8) scales and the QLQ-MY20 future perspective scale (11.9; 95% CI, 10.0-13.9). By contrast, the 34 nonresponders (29.1%) reported numerical worsening on most scales, with nominal statistically significant worsening on the QLQ-C30 fatigue scale and the EQ-5D-3L VAS.
The authors cautioned that the single-arm, open-label design, the shrinking evaluable population over time, and the assumption that missing assessments were missing at random limit interpretation, and that the findings should be considered within the context of patients who remained on treatment. These patient-reported data complement previously published LINKER-MM1 efficacy results, in which linvoseltamab elicited an objective response rate of 71%, with 52% of patients achieving a complete response or better; those results supported the agent’s FDA approval for patients who have received at least 4 previous lines of therapy.2
