Background
Randomized phase 3 trial of 559 patients with relapsed/refractory multiple myeloma with measurable disease who had received 1-3 prior regimens including a lenalidomide-containing regimen, comparing pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd).
Interventions and follow up
Arm A (PVd): Pomalidomide 4 mg PO D1-14 + bortezomib + dexamethasone, Q21D until progression or unacceptable toxicity
Arm B (Vd): Bortezomib + dexamethasone only, until progression or unacceptable toxicity
Backbone dosing: Bortezomib SC (post-amendment)/IV 1.3 mg/m2 D1,4,8,11 (C1-8), D1,8 (C9+); dexamethasone PO 20 mg (10 mg if >75 yr) on bortezomib days
Primary endpoint: PFS
Median follow-up: 15.9 months
Arm B (Vd): Bortezomib + dexamethasone only, until progression or unacceptable toxicity
Backbone dosing: Bortezomib SC (post-amendment)/IV 1.3 mg/m2 D1,4,8,11 (C1-8), D1,8 (C9+); dexamethasone PO 20 mg (10 mg if >75 yr) on bortezomib days
Primary endpoint: PFS
Median follow-up: 15.9 months
Results
Median PFS: 11.2 months (PVd) vs 7.1 months (Vd); HR 0.61, 95% CI 0.49-0.77, P<.001
Benefit consistent across lenalidomide-refractory subgroups
Benefit consistent across lenalidomide-refractory subgroups
Adverse events
Hematologic (grade ≥3): Neutropenia 42% (PVd) vs 9% (Vd); thrombocytopenia 27% vs 29%
Non-hematologic (grade ≥3): Infection 31% vs 18%; peripheral sensory neuropathy 8% vs 4%; pulmonary embolism 4% vs <1%
Non-hematologic (grade ≥3): Infection 31% vs 18%; peripheral sensory neuropathy 8% vs 4%; pulmonary embolism 4% vs <1%
Conclusions
PVd significantly improved progression-free survival over Vd in lenalidomide-exposed relapsed/refractory multiple myeloma, supporting the addition of pomalidomide in this setting.
Key Limitations
Comparator Vd is less active than current triplet standards, potentially overstating relative benefit. Higher rates of neutropenia and infection with PVd. Median follow-up was short for mature OS, which was not significantly different at this analysis.
Clinical Context
OPTIMISMM supported FDA approval of pomalidomide in combination with bortezomib and dexamethasone for relapsed/refractory multiple myeloma after ≥1 prior regimen including lenalidomide and a proteasome inhibitor. PVd is a recognized triplet option in the early-relapse, lenalidomide-exposed setting per ASCO and ESMO guidance.