PB2148 POMALIDOMIDE + BORTEZOMIB + LOW‐DOSE DEXAMETHASONE IN JAPANESE PATIENTS WITH RELAPSED REFRACTORY MULTIPLE MYELOMA: A SUBGROUP ANALYSIS OF THE PHASE 3 OPTIMISMM TRIAL
Authors: Matsue K. , Sunami K. , Suzuki K. , Takezako N. , Shinagawa A. , Sakurai S. , Tamakoshi H. , Biyukov T. , Peluso T. , Richardson P. 
Published: June 2019

Background:

The immunomodulatory agent pomalidomide (POM) in combination with dexamethasone (DEX) is approved in Japan for the treatment (Tx) of relapsed refractory multiple myeloma. Results from the multicenter phase 3 OPTIMISMM trial (NCT01734928) demonstrated a significantly improved progression‐free survival (PFS; median 11.2 vs 7.1 mos, HR, 0.61, P < .0001) with pomalidomide, bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) in the intent‐to‐treat population of 100% LEN pretreated patients (pts; 70% LEN refractory) who had 1‐3 prior regimens.

Aims:

To compare the safety and tolerability of PVd vs Vd in Japanese pts enrolled in OPTIMISMM.

Methods

Eligible pts were randomized 1:1 to PVd or Vd to receive 21‐day cycles (C) of POM 4 mg/day, days 1‐14 (PVd arm only), bortezomib (BORT) 1.3 mg/m2, days 1, 4, 8, and 11 C1‐8 and on days 1 and 8 C9+, and DEX 20 mg/day (10 mg/day if > 75 yrs), days of and after BORT.

Results:

Seventeen pts from Japan were enrolled in the OPTIMISMM trial (N = 559). Pts were randomized to PVd (n = 12) or Vd (n = 5); 13 pts (76%) were LEN refractory (8 PVd; 5 Vd). Median age was 72 yrs overall and 42% vs 20% of pts were female. Most patients in the PVd and Vd arms received 1 prior line of therapy (67% vs 60%) and prior BORT (67% vs 60%). Tx is ongoing in 7 vs 1 pt; 4 vs 3 pts discontinued due to progressive disease. Median Tx duration was 14.5 vs 4.0 mos. Median PFS was 17.6 with PVd vs 4.4 mos with Vd and overall response rate was 100% vs 60%, respectively; median follow‐up 14.8 mos. 12‐month overall survival rate was 100% in both arms. Median time to response was 0.8 vs 1.5 mos, median duration of response was 16.8 vs 7.4 mos. Grade 3 or 4 treatment‐emergent adverse events (TEAEs) included infections (5 vs 2 pts), neutropenia (6 vs 0 pts), thrombocytopenia (2 vs 1 pt), and anemia (0 vs 1 pt) with PVd vs Vd. No pts discontinued PVd due to TEAEs; 1 discontinued Vd due to bronchitis. A total of 10 pts (83%) in the PVd vs 4 (80%) in the Vd arm had dose reductions due to ≥ 1 TEAE, primarily due to peripheral sensory neuropathy (4 vs 3 pts). Five pts had their POM dose reduced due to ≥ 1 TEAE, which included thrombocytopenia (2 pts) and 1 each of dermatitis, rash, diarrhea, pneumonia, dehydration, peripheral neuropathy, and renal impairment. Dose interruptions due to ≥ 1 TEAE occurred in 11 pts (92%) in the PVd arm vs 4 pts (80%) in the Vd arm, mostly due to infections (7 vs 2 pts) and sensory neuropathy (3 vs 4 pts). Eleven pts had their POM dose interrupted, mainly due to infections (7 pts), including pneumonia (3 pts) bronchitis (2 pts), and influenza (2 pts). Other TEAEs that led to POM dose interruptions included 1 each of muscle abscess, upper respiratory tract infection, neutropenia, thrombocytopenia, hematuria, renal impairment, dermatitis, rash, diarrhea, humerus fracture, dehydration, and oropharyngeal pain.

Summary/Conclusion:

Efficacy outcomes demonstrate a clinical benefit with PVd vs Vd in a highly LEN‐refractory (76%) Japanese subgroup and are consistent with those reported in the overall OPTIMISMM population. Of note, PVd led to a 100% ORR. Toxicities were managed with dose reductions and interruptions; no pts discontinued PVd due to TEAEs.