Karlin, Lionel

ABSTRACTObjectivesThis final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.MethodsKey scales from the EORTC QLQ‐C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.ResultsThe intent‐to‐treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D‐Rd‐treated patients showed improvements from baseline that were sustained over 5 years in the intent‐to‐treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D‐Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16–2.91]), physical functioning (1.93 [1.18–3.14]), pain (1.41 [0.90–2.22]), and fatigue (2.00 [1.24–3.23]). Greater proportions of patients with bone lesions improved with D‐Rd versus Rd on GHS and physical functioning.ConclusionsIn transplant‐ineligible patients with NDMM, D‐Rd improved health‐related quality of life over a 5‐year period versus Rd. Trial Registration: ClinicalTrials.gov: NCT02252172

AbstractDeeper responses are associated with longer survival in multiple myeloma (MM); however, limited data exist on the impact of response kinetics on outcomes. We investigated progression‐free survival (PFS) and duration of response (DOR) by response depth and in early (best confirmed response 0–4 months; n = 424) versus late responders (best confirmed response >4 months; n = 281). Newly diagnosed patients enrolled in TOURMALINE‐MM2 receiving ixazomib‐lenalidomide‐dexamethasone (IRd) (n = 351) or placebo‐Rd (n = 354) were evaluated post hoc. Deeper responses were associated with longer PFS (complete response [CR] not reached [NR], very good partial response [VGPR] 37.2 months, partial response [PR] 16.4 months) and DOR (CR NR, VGPR 42.6 months, PR 15.4 months). Among patients with a PFS (n = 511) or DOR (n = 484) of ≥6 months who achieved ≥PR, median PFS was prolonged among late versus early responders receiving IRd (59.7 vs. 17.9 months) or placebo‐Rd (56.6 vs. 12.4 months), as was median DOR (IRd, NR vs. 20.9 months; placebo‐Rd, 58.2 vs. 11.7 months). While the treatment paradigm for newly diagnosed MM is treatment to progression, our findings suggest slowness of response to a proteasome inhibitor‐immunomodulatory drug‐steroid combination is not a negative predictor of outcome.

Abstract Introduction: Depth of response is associated with long-term outcomes in multiple myeloma (MM); however, the effect of response kinetics on outcomes in NDMM is variable and less clear. Although some studies have shown that achieving a ≥very good partial response (VGPR) at 4 months (mos) from diagnosis is associated with increased overall survival (Garderet Leukemia 2018), other reports have shown worse outcomes in pts with early vs late responses (Yan Blood Adv 2019). The double-blind, randomized TOURMALINE-MM2 (NCT01850524) trial (Facon Blood 2021) showed a clinical meaningful progression-free survival (PFS) benefit with IRd vs pbo-Rd (median 35.3 vs 21.8 mos; hazard ratio, 0.830; 95% confidence interval, 0.676-1.018; P=0.073; median follow-up, 53.3 and 55.8 mos, respectively) in NDMM pts. Safety data were consistent with the established toxicity profile of IRd. We evaluated PFS and duration of response (DOR) by depth of best confirmed response and time to best response in TOURMALINE-MM2. Methods: Pts were randomized to receive oral ixazomib 4 mg (n=351) or placebo (n=354) on days 1, 8, and 15, plus oral lenalidomide 25 mg (10 mg if creatinine clearance ≤60 mL/min) on days 1-21 and oral dexamethasone 40 mg (20 mg in pts aged &gt;75 years) on days 1, 8, 15, and 22 in 28-day cycles. After 18 cycles, treatment was continued without dexamethasone and reduced doses of ixazomib (3 mg) and lenalidomide (10 mg) until progressive disease (PD)/toxicity. Response assessments were performed every cycle until PD, or every 4 weeks in pts who discontinued treatment prior to PD. PFS and DOR were analyzed post-hoc in subgroups defined by depth of response and in subgroups defined by time to best confirmed response; 'early' and 'late' responses were defined by time to best confirmed response of 0-4 and &gt;4 mos, respectively (additional analyses were performed by time to best confirmed response of 0-6 and &gt;6 mos). Pts in either subgroup could have recorded an initial response prior to their best response. PFS and DOR were evaluated from randomization to progression and time of initial response to progression, respectively. To address potential guarantee-time bias in the PFS analysis, and to eliminate potential bias due to transient responses in DOR analysis, sensitivity analyses were conducted in pts with PFS / DOR of ≥6 mos. Results: Among the 705 pts in the intention-to-treat (ITT) population, 20% (26% IRd vs 14% placebo-Rd) had a best confirmed response of complete response (CR) or stringent CR, 35% (37 vs 34%) had VGPR, 26% (19 vs 32%) had PR, 10% (9 vs 10%) had stable disease (SD), 3% (1 vs 4%) had PD. 7% (8 vs 6%) of pts were not evaluable. In a pooled analysis of both arms, achieving a deeper response was associated with longer PFS (Figure, A) and DOR (median not reached [NR], 42.8, and 15.0 mos for pts with ≥CR, VGPR, and PR, respectively). In 570 pts with ≥PR (288 IRd; 282 pbo-Rd), 152 (53%) and 136 (47%) in the IRd arm and 143 (51%) and 139 (49%) pts in the pbo-Rd arm were defined as early (0-4 mos) and late (&gt;4 mos) responders, respectively. For early vs late responders, 46% vs 40% were aged ≥75 years, 21% vs 12% had International Staging System stage III MM, and 44% vs 33% had expanded high-risk cytogenetic abnormalities. Median PFS was prolonged among late vs early responders with IRd (65.7 vs 21.2 mos) and pbo-Rd (62.6 vs 18.2 mos), as was median DOR (IRd, NR vs 22.6 mos; pbo-Rd, 64.1 vs 17.2 mos). The PFS sensitivity analysis among pts with PFS of ≥6 mos confirmed the association of late response with improved outcomes; among late vs early responders achieving ≥PR, median PFS was 65.7 vs 23.9 mos with IRd and 62.6 vs 18.4 mos with pbo-Rd (Figure, B), and among late vs early responders achieving ≥VGPR, median PFS was 65.7 vs 35.3 mos with IRd and 64.4 vs 21.7 with pbo-Rd. Conclusions: Achieving a deeper response was associated with prolonged PFS and DOR in NDMM patients in TOURMALINE-MM2. PFS benefit on the ITT analysis was driven by the higher rates of deep responses (≥VGPR) with IRd vs pbo-Rd. PFS and DOR were also longer in pts achieving a late vs early best confirmed response of ≥PR or ≥VGPR. Consistent with results from a similar analysis in relapsed/refractory MM in the TOURMALINE-MM1 trial (Garderet Leukemia 2018), our findings support the continuation of therapy with the aim of achieving a deeper response over time. Additional sensitivity analyses will be presented. Figure 1 Figure 1. Disclosures Richardson: Sanofi: Consultancy; AstraZeneca: Consultancy; Celgene/BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Oncopeptides: Consultancy, Research Funding; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; Janssen: Consultancy; Takeda: Consultancy, Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding. Venner: Takeda: Honoraria; BMS: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Bahlis: GlaxoSmithKline: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Consultancy; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. White: Amgen: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Forus: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Karlin: Celgene-BMS: Honoraria, Other: member of advisory board; Sanofi: Honoraria; oncopeptide: Honoraria; Janssen: Honoraria, Other: member of advisory board, travel support; Abbvie: Honoraria; GSK: Honoraria, Other: member of advisory board; Amgen: Honoraria, Other: travel support and advisory board ; Takeda: Honoraria, Other: member of advisory board. Rigaudeau: Takeda: Membership on an entity's Board of Directors or advisory committees. Suzuki: Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; ONO: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Abie: Honoraria; Janssen: Consultancy, Honoraria. Shibayama: Mundi Pharma: Honoraria; Otsuka: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Nippon Shinyaku: Honoraria; Fujimoto: Honoraria; Daiichi Sankyo: Honoraria; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Essentia Pharma Japan: Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Avvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Celgene: Research Funding. Zhang: Takeda: Current Employment. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Twumasi-Ankrah: Takeda: Current Employment. Labotka: Takeda: Current Employment. Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Fresenius-Kabi: Membership on an entity's Board of Directors or advisory committees; Coherus: Membership on an entity's Board of Directors or advisory committees; McKesson: Current Employment, Current equity holder in publicly-traded company; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb (Celgene): Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Lonial: AMGEN: Consultancy, Honoraria; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Honoraria. Kumar: Antengene: Consultancy, Honoraria; Carsgen: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Moreau: Amgen: Honoraria; Oncopeptides: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria. OffLabel Disclosure: Use of the oral proteasome inhibitor ixazomib in newly diagnosed multiple myeloma patients who are ineligible for transplant.

Abstract Continuous lenalidomide-dexamethasone (Rd)-based regimens are among the standards of care in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. The oral proteasome inhibitor ixazomib is suitable for continuous dosing, with predictable, manageable toxicities. In the double-blind, placebo-controlled TOURMALINE-MM2 trial, transplant-ineligible NDMM patients were randomized to ixazomib 4 mg (n = 351) or placebo (n = 354) plus Rd. After 18 cycles, dexamethasone was discontinued and treatment was continued using reduced-dose ixazomib (3 mg) and lenalidomide (10 mg) until progression/toxicity. The primary endpoint was progression-free survival (PFS). Median PFS was 35.3 vs 21.8 months with ixazomib-Rd vs placebo-Rd, respectively (hazard ratio [HR], 0.830; 95% confidence interval, 0.676-1.018; P = .073; median follow-up, 53.3 and 55.8 months). Complete (26% vs 14%; odds ratio [OR], 2.10; P &lt; .001) and ≥ very good partial response (63% vs 48%; OR, 1.87; P &lt; .001) rates were higher with ixazomib-Rd vs placebo-Rd. In a prespecified high-risk cytogenetics subgroup, median PFS was 23.8 vs 18.0 months (HR, 0.690; P = .019). Overall, treatment-emergent adverse events (TEAEs) were mostly grade 1/2. With ixazomib-Rd vs placebo-Rd, 88% vs 81% of patients experienced grade ≥3 TEAEs, 66% vs 62% serious TEAEs, and 35% vs 27% TEAEs resulting in regimen discontinuation; 8% vs 6% died on study. Addition of ixazomib to Rd was tolerable with no new safety signals and led to a clinically meaningful PFS benefit of 13.5 months. Ixazomib-Rd is a feasible option for certain patients who can benefit from an all-oral triplet combination. This trial was registered at www.clinicaltrials.gov as #NCT01850524.

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.

8528 Background: RRMM patients (pts) who fail lenalidomide (LEN) and bortezomib (BORT) have poor prognosis. High-risk cytogenetics predict shorter survival. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT and high-risk cytogenetics. MM-003 is an open-label, multicenter, phase III trial comparing POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT treatment (Tx) and have progressed on their last therapy. Methods: Pts must have been refractory to the last prior Tx (progressive disease [PD] during or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-day cycles). Tx continued until PD or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS and AEs. This analysis examined pts meeting modified high-risk cytogenetic criteria—del(17p13) and/or t(4p16/14q32). Results: 302 pts received POM + LoDEX, and 153 pts received HiDEX. 225 and 107 pts, respectively, were evaluable for cytogenetics. Baseline characteristics were similar. Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX, regardless of cytogenetic risk (Table). The most common grade 3/4 AEs were neutropenia, anemia, and infection (Table). Discontinuation due to AE was low: 4% vs. 6% (high risk) and 10% vs. 4% (standard risk). Conclusions: Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX in pts with cytogenetically-defined high-risk disease, consistent with results from the intent-to-treat population. Tolerability was acceptable. POM + LoDEX should be considered a new Tx option in pts failing LEN and BORT. Clinical trial information: NCT01311687. [Table: see text]

8527 Background: Pts who have exhausted lenalidomide (LEN) and bortezomib (BORT) treatment (Tx) have a poor prognosis. A significant proportion of pts have RI with increasing incidence during disease course. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT, including those with RI. MM-003 is an open-label, multicenter, phase 3 trial comparing POM + LoDEX vs HiDEX in RRMM pts who failed LEN and BORT and progressed on their last Tx. Methods: Pts must have failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination) and must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days). Pts with creatinine clearance (CrCl) < 45 mL/min were excluded. Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) qw; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-D cycles). Tx continued until PD or unacceptable adverse event (AE). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and AEs. This analysis examined pts with or without moderate RI (CrCl < 60 vs ≥ 60mL/min). Results: 302 pts received POM + LoDEX; 153 pts received HiDEX, 31% and 39% had moderate RI, respectively. Pts with moderate RI were more likely to be older (64% vs 36% aged > 65 y) vs no RI. Median follow-up was 4 mo. Median PFS and OS were significantly longer with POM + LoDEX vs HiDEX regardless of RI (Table). Similar AE rates for POM + LoDEX as well as HiDEX Tx were seen in pts with and without moderate RI (Table). Discontinuation due to AE was 5% vs 7% (no moderate RI) and 11% vs 5% (moderate RI). Conclusions: POM + LoDEX significantly extended PFS and OS vs HiDEX in pts with or without moderate RI. Tolerability of POM + LoDEX was acceptable across subgroups, with few discontinuations due to AE. Clinical trial information: NCT01311687. [Table: see text]

Abstract Introduction Few treatments options are available for patients (pts) with relapsed/refractory multiple myeloma (RRMM) who have previously been treated with lenalidomide (LEN) and bortezomib (BORT), and their prognosis is poor. Pomalidomide (POM) is a distinct IMiD® immunomodulatory agent with a mechanism of action consisting of direct anti-myeloma, stromal-support inhibitory, and immunomodulatory effects. In randomized phase 2 and 3 trials (MM-002 and MM-003), POM plus low-dose dexamethasone (POM+LoDEX) demonstrated marked efficacy in RRMM pts who had received multiple prior therapies, including LEN and BORT. This side-by-side analysis presents the most recent survival and safety data from these trials. Methods The MM-002 and MM-003 trials enrolled pts with ≥ 2 prior therapies, including LEN and BORT. In MM-002, pts received POM (4 mg/day on days 1–21 of each 28-day cycle) alone or in combination with LoDEX (40 mg/week). In MM-003, pts were randomized 2:1 to receive POM+LoDEX or high-dose DEX alone (HiDEX) (40 mg/days 1–4, 9–12, 17–20 in a 28-day cycle); HiDEX was chosen as the comparator to isolate the effects of POM, as at the time of trial design it was the standard salvage therapy for heavily pretreated pts. Thromboprophylaxis was required for all pts treated with POM and pts at high risk of developing venous thromboembolism. Data cutoff was February 1, 2013 for MM-002 and March 1, 2013 for MM-003. The primary endpoint in both trials was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rates, duration of response, and safety. Results In each study, pts had received a median of 5 prior therapies (range 1-17), and all pts had received prior LEN and BORT. In MM-002, 113 pts were treated with POM+LoDEX and 108 were treated with POM alone (60% of POM alone pts subsequently received DEX). A total of 79% of pts were LEN refractory; 62% were refractory to both LEN and BORT; and 35% had received LEN as their last prior therapy. With a median follow-up of 14.2 months (mos), median PFS was 4.2 mos, OS was 16.5 mos, and overall response rate (ORR, defined as at least a partial response) was 33% with POM+LoDEX (Table 1). In MM-003, 302 pts were treated with POM+LoDEX and 153 pts were treated with HiDEX (50% of HiDEX pts subsequently received POM). A total of 94% of pts were LEN refractory; 74% were both LEN and BORT refractory; and 29% had received LEN as their last prior therapy. Survival outcomes were similar in MM-003; with a median follow-up of 10 mos, median PFS was 4.0 mos, OS was 12.7 mos, and ORR was 31% with POM+LoDEX. In both trials, LEN as last prior therapy did not impact response, PFS, or OS vs the overall population. Commonly observed adverse events (AEs) are presented in Table 2 for pts treated with POM+LoDEX. Grade 3 and 4 neutropenia was 28% and 13% in MM-002, and 26% and 22% in MM-003 for the POM+LoDEX arms, respectively. AEs were generally manageable for POM+LoDEX in MM-002 and MM-003 with dose interruptions (67% for both) and reductions (29% and 26%, respectively), and standard supportive care, including growth factor support (46% and 43%), red blood cell transfusions (45% and 49%), platelet transfusions (14% and 20%), and anti-infective agents (89% in both trials). Rates of POM discontinuation due to treatment-related AEs were low (2–4% with POM+LoDEX). In MM-002 and MM-003, 49% and 51% of pts in the POM+LoDEX arms experienced neutropenia of any grade. With appropriate AE management, 9% and 23% had dose interruptions, 4% and 8% had dose reductions, and 1 pt in both MM-002 and MM-003 discontinued due to neutropenia. Febrile neutropenia developed in 3% and 10% of pts; 1% and 4% had dose interruptions, 0% and 2% had dose reductions, and no pts discontinued due to febrile neutropenia in the MM-002 and MM-003 studies, respectively. The majority of infections occurred in the absence of neutropenia of any grade (54% in MM-002 and 66% in MM-003). The rate of POM discontinuation due to infection was low (1% in MM-002 and 2% in MM-003). Conclusion In both the MM-002 and MM-003 trials, POM+LoDEX consistently extended PFS in advanced RRMM pts. PFS, OS, and ORR were not negatively impacted in patients who were refractory to LEN or BORT, even as last prior therapy. Both trials demonstrated that with dose modifications and supportive care POM was well tolerated, leading to few discontinuations. POM+LoDEX should be considered a standard of care for pts with advanced RRMM who have exhausted LEN and BORT. Disclosures: Siegel: Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Richardson:Millennium: Membership on an entity’s Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees. Dimopoulos:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Song:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vij:Onyx: Consultancy, Research Funding; Millenium: Speakers Bureau; Celgene Corporation: Consultancy, Research Funding, Speakers Bureau. Bahlis:Celgene Corporation: Consultancy, Honoraria, Research Funding. Baz:Millenium: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Celgene Corporation: Research Funding. Hofmeister:Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Weisel:Celgene Corporation: Consultancy, Honoraria, Research Funding. Jagannath:Millennium: Honoraria; Celgene Corporation: Honoraria. Lonial:Millennium: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Sanofi: Consultancy; Onyx: Consultancy; Celgene Corporation: Consultancy. Delforge:Celgene Corporation: Honoraria. Talpaz:Ariad, Sanofi, Novartis: Membership on an entity’s Board of Directors or advisory committees; Ariad, Novartis, BMS, Pfizer: Speakers Bureau; Ariad, BMS, Sanofi, INCYTE: Research Funding. Moreau:Celgene Corporation: Honoraria, Speakers Bureau. San Miguel:Jansen, Celgene Corporation, Onyx, Novartis, Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Karlin:Janssen: Honoraria; Celgene Corporation: Consultancy, Expert board committee Other, Honoraria. Goldschmidt:Celgene Corporation, Janssen, Novartis: Consultancy, Honoraria, Research Funding. Oriol:Celgene Corporation: Consultancy. Alegre:Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Cavo:Millennium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Martinez-Lopez:Celgene Corporation: Honoraria, Research Funding. Lacy:Celgene Corporation: Research Funding. Chen:Celgene Corporation: Employment, Equity Ownership. Casey:Celgene Corporation: Employment, Equity Ownership. Sternas:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Jacques:Celgene Corporation: Employment, Equity Ownership. Anderson:Onyx: Consultancy, Equity Ownership; Gilead: Consultancy, Equity Ownership; sanofi aventis: Consultancy, Equity Ownership; Oncopep: Consultancy, Equity Ownership; Acetylon: Consultancy, Equity Ownership; Celgene Corporation: Consultancy, Equity Ownership.

Background:MAIA, an ongoing phase 3 trial of transplant‐ineligible patients with NDMM, demonstrated significant improvement in progression‐free survival with D‐Rd vs Rd alone. Assessment of patient‐reported outcomes (PRO) alongside efficacy endpoints provides patient perspective on their quality of survival and overall value of health‐related quality of life (HRQoL) while on treatments.Aims:To utilize PRO assessments as a tool in capturing the patient perspective on quality of survival and HRQoL changes in MAIA.Methods:The EORTC QLQ‐C30 and EQ‐5D‐5L questionnaires were completed by patients using an electronic device at baseline and every 3 months during treatment; interim results are presented for first 12 months. Treatment effects were assessed using repeated measures, mixed effects models and thresholds for clinically meaningful benefit were based on established criterion from the literature.Results:Compliance rates in completing the assessment tools were high and comparable at baseline (>90%) and through month 12 (>80%) for both groups (D‐Rd [n = 368]; Rd [n = 369]). Improvement in Global Health Status (GHS) occurred in both groups; however, for D‐Rd, significantly greater improvement was observed at cycle 3 (LS mean change; D‐Rd: 4.5 [95% CI: 2.4, 6.6], Rd: 1.5 [95% CI: −0.7, 3.7]; [p = 0.0454]) and increasing improvement occurred across all time points. Significant improvement and clinically meaningful benefit in HRQoL for D‐Rd was also observed in EQ‐5D‐5L Visual Analog Scale (VAS) scores (LS mean change; D‐Rd: 10.1 [95% CI: 8.1, 12.1], Rd: 4.9 [95% CI: 2.8, 7.0]; [p = 0.0002]). The VAS median time to worsening was 10 mo longer for D‐Rd. Of note, meaningful differences were observed between the treatment groups in two subscale scores, pain symptoms and cognitive functioning. Statistically significant less pain was reported early with D‐Rd (LS mean change at cycle 3; D‐Rd: −17.9 [95% CI: −20.7, −15.0], Rd: −11.0 [95% CI: −14.0, −8.1]; [p = 0.0007]); clinically meaningful reduction in pain symptoms was sustained with D‐Rd. There was a decline in cognitive functioning through Cycle 12 in both treatment arms with the peak difference occurring at Cycle 9, but mean differences between groups were not statistically significant.Summary/Conclusion:Faster and sustained improvement in patients treated with D‐Rd was observed using HRQoL assessments compared with Rd, with similar findings reflected across the pain subscale.