Background: Intravenous DARA (DARA IV) is approved for the treatment of MM. In Part 2 of PAVO, DARA SC, a concentrated, pre-mixed SC co-formulation of DARA and recombinant human hyaluronidase PH20 (rHuPH20), was well tolerated, with a low infusion-related reaction (IRR) rate, and showed consistent serum concentrations and similar efficacy to DARA IV in RRMM pts. In PAVO Part 3, we evaluated the safety of pre- and post-dose corticosteroid tapering during DARA SC administration. Methods: RRMM pts with ≥2 prior lines of treatment, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), received DARA SC (DARA 1,800 mg + rHuPH20 30,000 U in 15 mL) by manual SC injection per approved IV monotherapy dosing schedule. Pts received a 3-week (wk) tapering schedule (corticosteroid-free by Cycle [C] 1 Day [D] 22), with methylprednisolone (MP) given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg; C1D15, 30 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day; C1D15, 20 mg for 1 day), or a 2-wk tapering schedule (corticosteroid-free by C1D15), with MP given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg) and PO post-dose (C1D1, 20 mg for 2 days; C1D8, 20 mg for 1 day). Results: Pts (3-wk group, n = 15; 2-wk group, n = 15) received a median of 2 (range: 2-7) prior lines of therapy, with 37% refractory to a PI and an IMiD. The 3-wk and 2-wk groups received a median (range) of 14 (2-19+) and 8 (2-16+) DARA SC doses without corticosteroids, respectively. No IRRs were reported in the 3-wk group. 3 pts (20%) in the 2-wk group experienced IRRs on C1D1 (grade 3 hypertension, grade 2 chills, grade 1 pyrexia, grade 1 oropharyngeal pain, and grade 1 tachycardia). IRRs occurred within 2 h of the first DARA SC administration; no IRRs were reported at later administrations. Most common (≥25%) treatment emergent adverse events (TEAEs) were upper respiratory tract infection (40%) and fatigue and nausea (27% each). Most common (≥5%) grade 3/4 TEAEs were anaemia, lymphopenia, neutropenia, and hypertension (7% each). At median follow-up of 6.8 mo (3-wk group) and 2.4 mo (2-wk group), the overall response rates were 40% (95% CI, 16-68%) and 27% (95% CI, 8-55%) and ≥very good partial response rates were 13% (95% CI, 2-40%) and 7% (95% CI, 0-32%), respectively. Conclusions: Rapid corticosteroid tapering over 2 wks is safe in RRMM pts receiving DARA SC. These data help guide future DARA SC combinations (ie, T-cell redirectors, CAR-T, or checkpoint inhibitors), where limiting concurrent corticosteroids may be preferred. Clinical trial information: NCT02519452.