Background: Combination treatment (Tx) with IMiDs immunomodulatory agents and PIs demonstrated substantial efficacy in myeloma patients (pts) (Richardson, Blood, 2010). MM-005 was designed to identify the optimal PVD dose for a phase 3 trial (MM-007) comparing PVD vs. BORT + LoDEX in RRMM pts. A secondary objective examined subcutaneous (SC) BORT as part of PVD Tx. Methods: Eligible pts had 1-4 prior Tx lines, including ≥2 consecutive cycles (C) of LEN and a PI. Pts must have been LEN-refractory and PI-exposed but not BORT refractory. MTD was determined using a 3+3 design; an SC BORT cohort was added at the MTD. Tx continued until PD or unacceptable AE. MTD was the primary endpoint; additional endpoints included safety, overall response rate (ORR; ≥ partial response [PR]), time to response (TTR), duration of response (DoR), and pharmacokinetics. Results: The trial is fully enrolled (N=28): 22 pts in intravenous (IV) BORT and 6 pts in SC BORT cohorts. Median prior Tx was 2 (1-4). No dose-limiting toxicities (DLTs) were observed. Recommended PVD dose (21-day C) is POM 4 mg D1-14, BORT 1.3 mg/m² on D1, 4, 8, 11 for C1-8; D1, 8 for C9+, and LoDEX 20 mg (10 mg for pts > 75 y) on D1-2, 4-5, 8-9, 11-12 for C1-8; D1-2, 8-9 for C9+. Most common grade (Gr) 3-4 AEs included (IV cohorts): neutropenia (36%) and thrombocytopenia (27%); (SC cohort): 7 Gr 3 AEs occurred in one pt each; no Gr 4 AEs were observed. Peripheral neuropathy (PN) in IV cohorts was 0% (Gr 3-4), 14% (Gr 2), and 32% (Gr 1); 1 pt reported Gr 2 PN (SC cohort). No pt discontinued due to Tx-related AEs. ORR (IV cohorts) was 71% (38% ≥ very good PR [VGPR]), median TTR was 1 C, and median DoR was 11 C. Preliminary (median 5 C) ORR for SC pts was 67% (1 PR, 2 VGPRs, 1 complete response). 4 of 6 pts receiving BORT SC still remain on Tx; 1 of 4 pts has not yet responded. BORT administration route (IV/SC) did not impact POM exposure, which was within the range previously observed. Long-term follow-up will be presented. Conclusions: PVD was effective and well tolerated across all cohorts in LEN-refractory/BORT-exposed pts with no DLTs or discontinuations due to Tx-related AEs to date. PVD is now under evaluation in the MM-007 phase 3 trial. Clinical trial information: NCT01497093.