Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma

Br J Haematol. 2018 Jan;180(1):60-70. doi: 10.1111/bjh.14992. Epub 2017 Nov 21.

Abstract

Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m2 with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients. During Phase 1, the maximum tolerated dose of POM was 4 mg, and was used in Phase 2, which also required patients to be refractory to LEN. However, neutropenia ≥ grade 3 was observed in 10/17 (59%) patients, and the dose was lowered to 3 mg. Median PFS was 5·4 months (range, 0·3-29·0 + months). Overall response rates for patients in Phase 2 were 39% and 31% among subjects receiving POM at 3 mg and 4 mg, respectively, and clinical benefit rates were 51% and 44%, respectively. POM, PLD and DEX is a treatment option for relapsed/refractory MM patients including those who are refractory to LEN.

Keywords: Phase 1/2; immunomodulatory drugs; multiple myeloma; pegylated liposomal doxorubicin (PLD); pomalidomide.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology*
  • Polyethylene Glycols / administration & dosage
  • Recurrence
  • Retreatment
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • liposomal doxorubicin
  • Polyethylene Glycols
  • Thalidomide
  • Dexamethasone
  • Doxorubicin
  • pomalidomide