P-189: Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma (MM-014 phase 2 trial): a subanalysis of patients previously treated with lenalidomide and a proteasome inhibitor

Background Lenalidomide (LEN) with or without a proteasome inhibitor (PI) administered until disease progression is a standard treatment (Tx) approach for patients (pts) with newly diagnosed multiple myeloma (MM). Clinical trials investigating triplet therapies included few pts whose disease was relapsed/refractory to LEN after early-line Tx. The phase 2 MM-014 trial (NCT01946477) was designed to investigate outcomes with pomalidomide (POM)-based therapy immediately after first- or second-line LEN-based Tx failure in pts with relapsed/refractory MM (RRMM). In cohort B (n=112) of this trial, POM + dexamethasone (DEX) + daratumumab (DARA) demonstrated promising efficacy and safety with an overall response rate (ORR) of 78% and median progression-free survival (PFS) of 30.8 mo. Efficacy and safety in a subgroup of pts in cohort B previously exposed to LEN+PI are reported. Methods Pts with RRMM (1–2 prior Tx lines), LEN-based Tx for ≥2 consecutive cycles as most recent regimen, and disease progression during/after last line of Tx received POM+DEX+DARA (28-d cycles) until disease progression. POM 4 mg/d was given orally (PO) on d1–21; DEX 40 mg/d (20 mg/d in pts aged >75 y) PO on d1, 8, 15, and 22; and DARA 16 mg/kg IV on d1, 8, 15, and 22 of cycles 1–2, d1 and 15 for cycles 3–6, and d1 for cycles 7+. The primary endpoint was ORR; secondary endpoints included PFS and safety. Results In cohort B, 89/112 pts (79%; median age, 65 y) received prior LEN+PI. In this subgroup, 67 pts (75%) had LEN-refractory MM and 22 (25%) had LEN-relapsed MM; most pts (52 [58%]) received 1 vs 2 (37 [42%]) prior Tx lines. Median duration of Tx with POM, DEX, and DARA was 15.9, 14.0, and 16.1 mo, respectively. At a median follow-up of 28.4 mo (data cutoff Mar 2020), the ORR was 79% (≥very good partial response [VGPR], 55%). The ORR was 81% (≥VGPR, 63%) and 76% (≥VGPR, 43%) in pts with 1 vs 2 prior lines of Tx, respectively. Median duration of response and median PFS were not yet reached (1-y PFS rate, 74%). Infusion-related reactions occurred in 28% of pts and were primarily low grade (Gr). Overall, 98% of pts had ≥1 Gr 3/4 Tx-emergent adverse event. The most common Gr 3/4 hematologic events were neutropenia (64%; febrile, 12%), anemia (19%), and thrombocytopenia (13%). Gr 3/4 infections occurred in 40% of pts, including 16% with pneumonia. Conclusion POM+DEX+DARA administered immediately after LEN failure in a subgroup of pts previously treated with LEN+PI demonstrated a high response rate and a safety profile consistent with that in the overall cohort B population. Results support the use of POM-based therapy, integrating the monoclonal antibody DARA, as early as second line in pts with RRMM, potentially immediately after LEN Tx failure. Furthermore, the data support subsequent Tx with the same immunomodulatory agent class in a pt population with LEN-relapsed or -refractory MM. Previous presentation Bahlis NJ, et al. HemaSphere 2021;5:e482–483. EP1019.