A phase II study of pomalidomide, daily oral cyclophosphamide, and dexamethasone in relapsed/refractory multiple myeloma

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.

Keywords:

• Multiple myeloma
• pomalidomide
• IMiDs
• cyclophosphamide
• MYC
• immune microenvironment

Disclosures statement

The following authors have served as paid consultants from the identified companies: AC for Novartis, Celgene; SJ for Novartis, Celgene. SP has research support from Celgene and Karyopharm. SC, MW, WEP, and AT were Celgene employees at the time of the study. The following authors have no conflicts to disclose: OVO, HJC, NV, DM, JR, CI, KL, EF, ISM, JT, DV, EC, KZ, LL, GS, DTM, VL, SKS, AL.

Author contributions

AC provided investigation, conceptualization, methodology, analysis, resources, original draft, supervision review and edits of the manuscript. HJC, OVO, and SP provided analysis, investigation, resources, review and edits of the manuscript. AL, VL, DTM, SKS and OVO provided data analysis, creation of tables and figures for the correlative studies. NV provided formal analysis of the data, provision of study materials, research data management and creation of tables and figures, review and edits of the manuscript, and preparation of the data presentation. DM, JR, CI, KL, EF, ISM, JT, DV, EC, KZ, LL, GS, SC, MW, WEP and, AT provided research and investigation process, resources, review and edits of the manuscript, and visualization of the project. SJ, SP provided conceptualization, methodology, research and investigation process, review and edits of the manuscript, supervision, and funding acquisition of the project. All coauthors were provided final approval of the published version.

Additional information

Funding

This work was funded and supported by Celgene Pharmaceuticals.