PF595 POMALIDOMIDE + BORTEZOMIB + LOW‐DOSE DEXAMETHASONE AFTER ONE PRIOR LINE OF THERAPY IN PATIENTS WITH LENALIDOMIDE‐PRETREATED MULTIPLE MYELOMA: SUBGROUP ANALYSIS OF THE PHASE 3 OPTIMISMM TRIAL
Authors: Dimopoulos M. , Weisel K. , Moreau P. , Jr L.D. Anderson , White D. , Miguel J. San , Sonneveld P. , Engelhardt M. , Jenner M. , Corso A. , Dürig J. , Pavic M. , Salomo M. , Yu X. , Nguyen T. Vi , Bensmaine A. , Peluso T. , Zaki M. , Richardson P. 
Published: June 2019

Background:Lenalidomide (LEN) is an established treatment (Tx) option for newly diagnosed multiple myeloma; however, patients (pts) for whom LEN is no longer a Tx option, including those who have become refractory to LEN, represent a clinically relevant pt population that is growing globally. Results of the phase 3 registrational trial (San Miguel J, et al. Lancet Oncol. 2013;14:1055–1066) showing a significant improvement in progression‐free survival (PFS) and overall survival with pomalidomide (POM) + low‐dose dexamethasone (LoDEX) vs high‐dose dexamethasone in heavily pretreated (median of 5 prior regimens) pts with relapsed or refractory MM (RRMM), most (95%) of whom were refractory to LEN, led to the approval of POM + LoDEX in RRMM. Pomalidomide, bortezomib, and low‐dose dexamethasone (PVd) has demonstrated encouraging activity in early‐phase clinical trials in LEN‐refractory pts. In the phase 3 OPTIMISMM trial (NCT01734928), PVd demonstrated a significantly improved PFS compared with bortezomib and low‐dose dexamethasone (Vd) in intent‐to‐treat population of pts who received 1–3 prior regimens and were 100% LEN pretreated; 70% of pts were LEN refractory.Aims:To compare the efficacy and safety of PVd vs Vd in LEN‐refractory and LEN‐nonrefractory pts treated with 1 prior line of therapy (LOT).Methods:Pts were randomized 1:1 to receive PVd or Vd in 21‐day cycles: POM 4 mg/day on days 1–14 (PVd arm only); bortezomib (BORT) 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1–8 and on days 1 and 8 of cycles 9+; and DEX 20 mg/day (10 mg/day if aged > 75 yrs) on the days of and after BORT. The primary endpoint was PFS.Results:As of October 26, 2017, 226 out of 559 pts enrolled had 1 prior LOT (111 PVd; 115 Vd). Among these pts, 129 (57.1%) were LEN refractory (64 PVd; 65 Vd) and 97 (42.9%) were LEN nonrefractory (47 PVd; 50 Vd). In LEN‐refractory pts median age was 68.0 vs 69.0 yrs, 57.8% vs 58.5% were male, and 56.3% vs 47.7% had prior BORT in the PVd vs Vd groups. In LEN‐nonrefractory pts, median age was 66.0 vs 65.5 yrs, 63.8% vs 38% were male, and 66.0% vs 72.0% had prior BORT. After 1 prior LOT, PVd vs Vd significantly improved PFS (median, 17.8 vs 9.5 mos [P = .0276] in LEN‐refractory and 22.0 vs 12.0 mos [P = .0491] in LEN‐nonrefractory pts; Table 1); median follow‐up 16.4 mos. PVd also significantly improved ORR in LEN‐refractory and LEN‐nonrefractory pts compared with Vd (Table 1). In LEN‐refractory pts, the most common grade 3 or 4 treatment‐emergent adverse events (TEAEs) with PVd vs Vd were neutropenia (35.9% vs 12.9%), thrombocytopenia (17.2% vs 22.6%), and anemia (17.2% vs 8.1%); 29.7% vs 21.0% had grade 3 or 4 infections. Among LEN‐nonrefractory pts, the most common grade 3 or 4 TEAEs were neutropenia (36.2% vs 6.3%) and thrombocytopenia (23.4% vs 18.8%). Grade 3 or 4 infections occurred in 27.7% vs 8.3% of pts. LEN‐refractory pts had a median Tx duration of 9.7 with PVd vs 6.1 mos with Vd. In LEN‐nonrefractory pts, median Tx duration of Pvd vs Vd was 13.6 vs 6.6 mos.Summary/Conclusion:In LEN‐refractory and ‐nonrefractory pts after 1 prior LOT, PVd reduced the risk of progression and death by 45% and 46% vs Vd, respectively. Further, in both subgroups, second‐line Tx with PVd significantly improved ORR and led to deeper responses compared with Vd. TEAEs with PVd therapy were generally consistent with the known profiles of POM, BORT, and DEX. These data further demonstrate that PVd is effective and tolerable in pts for whom LEN is no longer a Tx option, including LEN‐refractory pts, supporting its use as second‐line therapy in RRMM.image