Patient-reported outcomes and actigraphy following in-class transition (iCT) from parenteral bortezomib (V) to oral ixazomib in newly diagnosed multiple myeloma (NDMM): Subgroup analysis of US MM-6 by race/ethnicity, renal function, and area income

Abstract Introduction: Prolonged parenteral treatment for multiple myeloma may expose patients (pts) to cumulative side effects that can significantly impact their quality of life (QoL). Pt-reported outcomes (PROs) are important in understanding the burden of treatment and the pt experience. US MM-6 (NCT03173092), a community-based phase 4 study, demonstrated the benefit of iCT from parenteral V-based induction to all-oral ixazomib/lenalidomide/dexamethasone (IRd) in facilitating long-term proteasome inhibitor-based therapy for pts with NDMM. We present US MM-6 PRO and actigraphy data among pt subgroups that are often underrepresented in clinical trials. Methods Transplant-ineligible/delayed transplant (≥24 months) pts with NDMM without progressive disease (PD) after 3 cycles of V-based induction were enrolled to receive oral IRd (≤39 cycles or until PD/toxicity). Electronic PROs (ePROs) were assessed via questionnaires: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), Treatment Satisfaction Questionnaire for Medication – 9 item version (TSQM-9), and EORTC QLQ – Myeloma Module (QLQ-MY20). Actigraphy data were collected via digital devices worn by pts. Not all study sites could accommodate the wearables/ePROs. Endpoints are reported for the US MM-6 intent-to-treat (ITT) population and by subgroups: racial/ethnic minorities (non-White race or Hispanic/Latino ethnicity); renal impairment (creatinine clearance ≤60 ml/min); and low area income (<$45K/year median household income associated with the clinical site zip code). All endpoints were analyzed descriptively. Results: At data cutoff (Oct 2024 [ePROs]; May 2024 [actigraphy]), of 140 pts with IRd treatment, 135 (41 [minority], 94 [non-minority]); 136 (40 [renal impairment], 96 [non-renal impairment]); and 140 (49 [low income], 91 [non-low income]) were included in the subgroups. Among 1037 EORTC QLQ-C30, 1116 TSQM-9, and 1046 EORTC QLQ-MY20 questionnaires issued to 55, 59, and 56 pts, 988, 1063, and 998 were completed, respectively, for an average compliance rate of 95%. Mean changes from baseline EORTC QLQ-C30 global health status scores across treatment cycles were mostly less than 10 (considered the minimal important difference) indicating overall maintenance of QoL. Mean changes from baseline in TSQM-9 scores were small over the course of treatment, indicative of overall treatment satisfaction. For the EORTC QLQ-MY20 questionnaire (item 43) measuring the burden of peripheral neuropathy (PN; scale of 1–4; higher scores indicate an increase in symptoms), the mean increase from baseline score was ≤0.7 across cycles, indicating that PN symptoms did not worsen much during IRd treatment. Results of questionnaires were generally consistent across subgroups; there was more variation for some subgroups (e.g., racial/ethnic minorities and renal impairment) in which the sample sizes were very small, resulting in wider 95% confidence intervals. Overall, 103 pts had available actigraphy data (27,447 total days). Of these, 24,863 days (91%) were considered compliant (≥12 hrs of wear per day and ≥14 days of wear per cycle). Mean (standard deviation [SD]) number of daily steps in the ITT population (n=94) was 3170 (2423); across subgroups, pts had a mean (SD) of 2610 (2436)/3448 (2422) steps (minority [n=23]/non-minority [n=66]); 3447 (2218)/3079 (2488) steps (renal impaired [n=25]/non-impaired [n=68]); and 3522 (2343)/3035 (2430) steps (low [n=31]/non-low income [n=63]). Mean (SD) daily active time was 0.43 (0.34) hrs (ITT); 0.33 (0.31)/0.47 (0.34) hrs (minority/non-minority); 0.45 (0.32)/0.42 (0.34) hrs (renal impaired/non-impaired); and 0.48 (0.33)/0.40 (0.33) hrs (low/non-low income). Mean (SD) daily sleep time was 7.55 (2.71) hrs (ITT); 7.97 (3.28)/7.29 (2.45) hrs (minority/non-minority); 7.16 (2.30)/7.68 (2.82) hrs (renal impaired/non-impaired); and 6.96 (2.60)/7.76 (2.71) hrs (low/non-low income). Conclusions: ePRO and actigraphy data collected in US MM-6 indicate that long-term treatment with all-oral IRd has minimal impact on health-related QoL or pt activity/sleep, including in pt subgroups typically underrepresented in clinical trials. ePRO collection in pts appears highly feasible according to the average compliance observed. For all ePRO outcomes, considering the relatively small sample sizes, which decreased over time, results for later cycles and subgroups should be interpreted with caution.