A phase II study of pomalidomide, daily oral cyclophosphamide, and dexamethasone in relapsed/refractory multiple myeloma
Oliver Van Oekelen, Samir Parekh, Hearn Jay Cho, Nivetha Vishnuvardhan, Deepu Madduri, Joshua Richter, Chun Ip, K. H. Vincent Lau, Erika Florendo, Ines Stefania Mancia, Joanne Thomas, Daniel Verina, Elaine Chan, Katarzyna Zarychta, Lisa La, Gina Strumolo, David T. Melnekoff, Violetta V. Leshchenko, Seunghee Kim‐Schulze, Suzana S. Couto, Maria Wang, William E. Pierceall, Anjan Thakurta, Alessandro Laganà, Sundar Jagannath, Ajai Chari
Abstract
Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD). Thirty-three patients were evaluable for efficacy and underwent 28-day cycles of pomalidomide (4 mg/day, D1-21), cyclophosphamide (50 mg b.i.d., D1-21) and weekly dexamethasone. All were lenalidomide-refractory and 55% were refractory to lenalidomide and proteasome inhibitor. ORR was 73%; median PFS and overall survival were 13.3 months and 57.2 months respectively. Grade 3/4 toxicities were primarily hematologic but manageable with dose reductions. Early disease progression correlated with MYC expression and flow cytometry demonstrates an activated microenvironment post-PCD. Addition of metronomic cyclophosphamide to pomalidomide and dexamethasone is a cost-effective, oral regimen with encouraging PFS.