Background : Transplant-ineligible Patients with relapsed/refractory multiple myeloma (RRMM) who failed both proteasome inhibitors and immunomodulators have a short life expectancy. Accordingly, effective third- or later-line therapy is needed for improving survival outcomes. Therefore, we planned to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCD) in elderly patients with RRMM who had failed both bortezomib and lenalidomide.

Methods : Between May 2015 and November 2017, a total of 55 patients were included in this study at 14 academic institutes in South Korea. The primary end-point of the study was the median progression-free survival (PFS), and the secondary end-points were the overall survival (OS), overall response rate (ORR), and toxicities. Eligible patients had received two or more previous lines of therapy, including bortezomib and lenalidomide in combination with bortezomib, melphalan, and prednisone (VMP) or lenalidomide and dexamethasone (RD). All patients had received both lenalidomide and bortezomib. Patients received the 28-day cycle of pomalidomide (4 mg/day on days 1-21, orally) plus dexamethasone (40 mg/day on day 1, 8, 15, and 22, orally). Dexamethasone dose was reduced to 20 mg/day in all patients older than 75 years. Oral cyclophosphamide (400 mg) was administered orally on days 1, 8, and 15 of the 28-day cycle.

Results : The median (range) age was 73.3 (64-86) years. All patients had received prior treatment with lenalidomide and bortezomib (100%). The ORR (PR and better) of all patients was 58.2%, while the clinical beneficial response rate (CBR), i.e., the ORR plus a minimal response (MR), was 72.7%. Complete response (CR) was observed in 7.3%, very good partial response (VGPR) in 21.8%, PR in 29.1%, MR in 14.5%, SD in 16.4%, and progressive disease in 7.3%. The time to the best response was 1.73 months (range 0.89-12.53 months). The median PFS and OS were 6.90 months (95% CI, 4.77-9.04 months) and 18.48 months (95% CI, 9.36-27.60 months), respectively. A better response including ≥VGPR and longer duration of therapy of ≥13 cycles were independent prognostic factors for PFS (P = 0.008 and P = 0.009, respectively). Longer duration of therapy and high risk of R-ISS (stage III) were independent risk factors for OS (P = 0.039 and P = 0.023, respectively). The incidence of grade 3-5 non-hematological toxicities including pneumonia, infection, and febrile neutropenia, was also relatively high (21.8%, 9.1%, and 10.9%, respectively).

Conclusions : PCD might be effective for for transplant-ineligible elderly patients with MM who had relapse and/or refractory to bortezomib and lenalidomide treatment in spite of relatively high toxicities. Therefore, active dose modification of pomalidomide and cyclophosphamide should be recommended to improve treatment outcomes and reduce toxicities at the beginning of the administration for transplant-ineligible elderly RRMM.


Yoon:Genentech, Inc.: Research Funding; MSD: Consultancy; Yuhan Pharma: Research Funding; Janssen: Consultancy; Novartis: Consultancy, Honoraria; Kyowa Hako Kirin: Research Funding; Amgen: Consultancy, Honoraria. Yoon:F. Hoffmann-La Roche Ltd: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.