HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH TRANSPLANT-INELIGIBLE OR TRANSPLANT-DEFERRED NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) IN THE PHASE 3 CEPHEUS TRIAL

Previous daratumumab clinical trials showed no detriment to health-related quality of life (HRQoL) with addition of daratumumab as part of a triplet or quadruplet treatment regimen. In the phase 3 CEPHEUS trial (NCT03652064), minimal residual disease negativity and progression-free survival improved with subcutaneous daratumumab plus bortezomib and Rd (DVRd) vs VRd in pts with newly diagnosed multiple myeloma (NDMM). Evaluate HRQoL of DVRd vs VRd in CEPHEUS. Pts had transplant-ineligible (TIE) or transplant-deferred (TD) NDMM, ECOG performance status ≤2, and International Myeloma Working Group frailty score ≤1. Pts were randomized 1:1 to DVRd or VRd. Patient-reported outcomes (PROs) were evaluated at baseline (BL), once each cycle to C8D1, and every 3rd C from C9D1 until disease progression. PROs included the European Organization for Research and Treatment of Cancer quality of life questionnaire core 30 (EORTC QLQ-C30), EORTC QLQ multiple myeloma 20 (EORTC QLQ-MY20), and the EuroQol 5-Dimension 5-Level (EQ-5D-5L). The intent-to-treat population had 395 pts (DVRd, n = 197; VRd, n = 198). Median follow-up was 58.7 months; 135 pts in the DVRd arm and 106 in the VRd arm were on study treatment at C36. Compliance was >85% at BL and >81% through C36 in both arms. For all questionnaires, BL means were comparable, and similar improvements in least square (LS) mean change from BL were seen across arms. At C36, the LS mean change from BL (95% CI) in EORTC QLQ-C30 global health status was 8.2 for DVRd and 8.5 for VRd with no apparent difference between arms. For EORTC QLQ-C30, the LS mean change from BL at C36 was 3.6 for DVRd and 5.1 for VRd (difference −1.5 [−6.4, 3.4], P = 0.54). For fatigue, these changes were −4.7 (−8.6, −0.7) for DVRd and −5.4 (−9.6, −1.2) for VRd (difference 0.7 [−4.9, 6.3], P = 0.80). For pain, reduction from BL was numerically higher with DVRd (−14.8) vs VRd (−8.7; difference −6.1 [−12.7, 0.5], P = 0.06). LS mean change from BL in EORTC QLQ-MY20 disease symptoms score at C36 was −8.4 for DVRd and −9 for VRd (difference 0.6 [−3.5, 4.7], P = 0.78). For EQ-5D-5L visual analogue scale (VAS) score, these changes were 7.3 () in DVRd and 5.6 () in VRd (difference 1.7 [−2.4, 5.7], P = 0.41). For all scales, a similar median time to worsening and time to improvement were observed across arms. PROs of the TIE subgroup had similar results. DVRd-treated pts in CEPHEUS had improved HRQoL and physical functioning as well as symptom (pain, fatigue, overall disease symptoms) reduction from BL. Improvements were similar vs VRd with no apparent differences between arms, indicating no detriment to HRQoL with addition of daratumumab. This study was funded by Johnson & Johnson. Medical writing support was provided by Shuang Li, PhD, of Eloquent Scientific Solutions, and funded by Johnson & Johnson.