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8035 Background: LYRA is a community practice-based, phase 2, single-arm study (NCT02951819) evaluating DARA + CyBorD as an immunomodulatory drug-sparing regimen in MM. The primary analysis demonstrated the safety and efficacy of DARA + CyBorD in newly diagnosed MM (NDMM) and relapsed MM (RMM), and an update showed that DARA maintenance therapy deepened responses. We present the final end-of-study analysis of LYRA. Methods: US pts aged ≥18 years with MM per IMWG criteria and ≤1 prior line of therapy received 4-8 induction cycles of DARA + CyBorD (cyclophosphamide 300 mg/m2 PO weekly [QW]; bortezomib 1.5 mg/m2 SC on Days [D] 1, 8, and 15; dexamethasone 40 mg PO or IV QW every 28 days; DARA IV 8 mg/kg on D1 and D2 of cycle [C]1, 16 mg/kg QW C1D8-C2, 16 mg/kg Q2W C3-6, and 16 mg/kg Q4W C7-8). After induction, eligible pts could receive autologous stem cell transplantation (ASCT). Pts received up to 12 maintenance cycles with DARA 16 mg/kg IV Q4W and were followed for up to 36 months after induction. Results: In total, 101 (NDMM, n = 87; RMM, n = 14) pts were enrolled; 36% of pts had high-risk cytogenetics. NDMM and RMM pts received a median of 6 and 8 induction cycles, respectively. Among NDMM pts, 44.8% (39/87) underwent ASCT and 72.4% (63/87) completed 12 months of maintenance. Rates of ≥VGPR and ≥CR were 82.1% and 48.7% in NDMM pts who underwent ASCT, and 70.2% and 29.8% in NDMM pts who did not (Table). With a median follow-up of 35.7 months, median progression-free survival (PFS) and overall survival (OS) were not reached for NDMM pts. Estimated 36-month PFS rates were 69.3% and 72.6% for NDMM pts who did and did not receive ASCT, respectively; estimated 36-month OS rates were 94.9% and 84.3% (Table). Among RMM pts, 7.1% (1/14) underwent ASCT and 50.0% (7/14) completed 12 months of maintenance; efficacy outcomes are shown in the Table. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 62.0% of all pts, with the most common (≥10%) being neutropenia (14.0%). Serious TEAEs occurred in 33.0% of pts, the most common being pneumonia (4.0%) and pulmonary embolism (3.0%). TEAEs led to death in 2.0% of pts, all unrelated to study treatment. Infusion-related reactions occurred in 56.0% of pts; the majority were mild (4.0% of pts had grade 3/4 events). Conclusions: DARA used for induction with CyBorD and maintenance as monotherapy resulted in durable, deep responses in pts with NDMM or RMM, with a 3-year PFS rate of 70% in NDMM irrespective of ASCT status. With longer follow-up, no new safety concerns were identified. Clinical trial information: NCT02951819. [Table: see text]

LBA3 Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures). Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy). Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (

8513 Background: Histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI) act synergistically through inhibition of the proteasome and aggresome pathways. We have previously reported t...

8012 Background: LY2127399 (LY) is a human mAb that neutralizes membrane-bound and soluble B cell activating factor (BAFF). LY has activity in xenograft models of multiple myeloma (MM) and is being...