Pomalidomide, cyclophosphamide, and dexamethasone for elderly patients with relapsed and refractory multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP-164 study)

Am J Hematol. 2020 Apr;95(4):413-421. doi: 10.1002/ajh.25726. Epub 2020 Jan 24.

Abstract

Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Drug Resistance, Neoplasm
  • Febrile Neutropenia / epidemiology
  • Febrile Neutropenia / etiology
  • Female
  • Frail Elderly
  • Frailty / complications
  • Frailty / diagnosis
  • Hematologic Diseases / chemically induced
  • Hematologic Diseases / epidemiology
  • Humans
  • Incidence
  • Infections / epidemiology
  • Kaplan-Meier Estimate
  • Lenalidomide / administration & dosage
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Myeloma Proteins / analysis
  • Prednisone / administration & dosage
  • Progression-Free Survival
  • Recurrence
  • Republic of Korea / epidemiology
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives

Substances

  • Myeloma Proteins
  • Thalidomide
  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide
  • pomalidomide
  • Lenalidomide
  • Melphalan
  • Prednisone