Background: Len-refractory pts have poor outcomes, highlighting an unmet medical need. In the phase 1b MMY1001 study (NCT01998971), D-Kd induced deep responses and was well tolerated in pts with relapsed MM. We examined the safety and efficacy of D-Kd in len-refractory pts. Methods: In total, 85 carfilzomib (carf)-naïve pts with 1-3 prior lines of therapy were enrolled. Pts received carf (20 mg/m² on Cycle 1 Day 1 [C1D1] and 70 mg/m² on C1D8+) on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg QW. DARA was given QW C1-C2, Q2W C3-C6, and Q4W thereafter; 10 pts received a standard first dose of DARA (16 mg/kg) on C1D1, and 75 pts received a split first dose of DARA (8 mg/kg on C1D1 and C1D2). Refractoriness was defined as progression ≤60 days of completion of last line of therapy. Results: Among len-refractory pts (n = 51) in the MMY1001 D-Kd arm, median age was 66 yrs (range 38-85 yrs). Pts had received a median of 2 (range 1-4) prior lines of therapy; 98% had received bortezomib (bort), 18% had received pomalidomide (pom), 43% were refractory to bort, and 18% were refractory to pom. In total, 20 pts (39%) discontinued due to progressive disease (26%), adverse events (AEs; 6%), pt withdrawal (6%), or physician decision (2%). The most common hematologic grade 3/4 treatment-emergent AEs (TEAEs; ≥10%) were thrombocytopenia (37%), anemia (29%), neutropenia (28%), and lymphopenia (26%). Infusion-related reactions were observed in 37% of pts (43% for standard first DARA dose; 36% for split first DARA dose); none were grade 3/4. With 8.3 months of median follow up, median PFS was 14.1 months (95% CI 9.4-not estimable); the 12-month PFS rate was 69% (95% CI 49-82). ORR and MRD-negative rates are summarized in the Table. Median time to MRD negativity (10^–5) was 5.1 months. Conclusions: The combination of DARA and weekly Kd was well tolerated and demonstrated promising efficacy in len-refractory pts. Updated data will be presented. Clinical trial information: NCT01998971

^aAmong response-evaluable pts who received > 2 cycles or discontinued treatment.