Pomalidomide, Cyclophosphamide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: A Retrospective Single Center Experience

Introduction: The response rate (partial remission and better) of pomalidomide and low dose dexamethasone in myeloma patients who received prior lenalidomide and bortezomib was 34% (Richardson P, Blood 2011, 118; abs 634). In order to increase the response rate of a pomalidomide based therapy, investigators commonly add oral weekly cyclophosphamide to pomalidomide and dexamethasone (PCD). We conducted a retrospective, single institution, study to analyse the efficacy and toxicity of the PCD combination for relapse/refractory patients.

Patients / Methods: Patients had relapsed/refractory myeloma. They received pomalidomide 4 mg PO D1-21, dexamethasone 40 mg PO D1-4 and D15-19 (20mg if older than 75 years) or 40 mg once a week and oral cyclophosphamide 300 mg on D1, 8, 15, 22 of a 28 days cycle. Treatment was given as a bridge to transplantation or until progression. Granulocyte colony stimulating factor support was allowed. Thrombosis and infectious prophylaxis were recommended. Responses were assessed per the IMWG criteria.

Results: Twenty patients were analyzed. The median age was 57 (range= 42 -76) years, and 9 were males (45 %). The immunoglobulin subtype was IgG 19, IgA 1. At diagnosis, the SD stage was I (73%) and II (27 %) and 5 missing values. The ISS score was I (50 %), II (30 %), III (20 %). The disease characteristics before PCD were: bone disease in 13 patients (93%, with 6 missing values), median calcemia was 2.3 micromol/L (range= 2.1- 2.6), hemoglobin was 11g/dL (range= 8-14), platelets were 178 000/mm3 (range=7-361), 10 % had a creatinine level >176 micromol/L (no hemodialysis was performed), elevated lactate dehydrogenase  (> 470 IU) in 5 cases (25 %), elevated C-reactive protein (> 5 IU), for 6 patients (40%, 5 missing values). The median time from diagnosis to current therapy was 4 years (range= 1-16 years). The median number of prior therapies was 4 (range= 2-6). Prior treatments were chemotherapy (9), thalidomide (10), lenalidomide (20), bortezomib (19), autologous stem cell transplantation (ASCT) (10), double ASCT (1). Five patients were bortezomib refractory and 4 were lenalidomide refractory. The median number of administered cycles was 4 (2-12). The confirmed response rate (more than PR) was 63 % and the median number of cycles to response 3 (range=1-9). The number of responders after the first cycle was 8/19 (42 %). The type of best response were: CR: 1 (5%), VGPR: 3 (16%), PR: 8 (42%), SD: 4 (21%), PD: 3 (16%). With a follow-up of 8.5 months, the median PFS at 1 year is 80.7 % (95% CI: [63.2-100]). Patients without relapse at follow-up are 13 (65%). The causes of PCD withdrawal are: scheduled ASCT (6, 46%), toxicity (3, 23%), disease progression (4, 31%). The treatments after PCD failure were ASCT (4, 21 %), IMiDs (7, 37 %), other (10, 53 %). Response (≥PR) to salvage treatment post PCD was 60 %. At the last follow-up, the status was n=19 alive, and 1 patient lost to follow up. Toxicity was mostly neutropenia (50 %) and one patient had pulmonary aspergillosis.

Conclusion: Toxicities were manageable and the PCD regimen had evidence of preliminary efficacy. Almost half of the patients could proceed to salvage ASCT. The IFM is currently conducting a phase II study analyzing the role of PCD for relapsing patients who were initially treated with bortezomib lenalidomide dex and had an ASCT upfront or delayed (IFM 2009/DFCI trial).