KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma

Clin Lymphoma Myeloma Leuk. 2021 Aug;21(8):526-535. doi: 10.1016/j.clml.2021.03.013. Epub 2021 Apr 6.

Abstract

Background: Patients with advanced/aggressive multiple myeloma have limited treatment options to achieve rapid disease control. In eligible patients, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide is often used. However, many patients are refractory to or have toxicities from bortezomib and there is a need for bridging therapy. We have used a modified regimen incorporating the second-generation proteasome inhibitor carfilzomib (carfilzomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide [KD-PACE]) instead of bortezomib for relapsed/refractory multiple myeloma.

Patients and methods: This 2-center retrospective study included consecutive patients receiving KD-PACE for relapsed or refractory multiple myeloma, plasma cell leukemia, or extramedullary myeloma. The primary outcome was the feasibility of KD-PACE as a bridging therapy to a more definitive treatment option.

Results: Fifty-two patients were included. The median age was 57 years, and 67% were male. Thirty-one patients were bridged with KD-PACE to autologous hematopoietic stem cell transplant (29%), allogenic hematopoietic stem cell transplant (27%), or a clinical trial (12%). Patients bridged to autologous hematopoietic stem cell transplant, allogenic hematopoietic stem cell transplant, or a clinical trial had a superior progression-free survival (8.3 months vs 2.3 months in the nonbridged group; P < .001) and overall survival (median, 16.7 months vs 4.3 months in the nonbridged group; P < .001). No unexpected toxicities occurred from the treatment regimen.

Conclusion: KD-PACE is a promising treatment option for select patients with advanced/aggressive forms of myeloma requiring rapid disease control before a more definitive salvage therapy such as auto/allotransplantation or a clinical trial.

Keywords: Allogenic; Carfilzomib; Clinical trial; Proteasome inhibitors; Transplantation.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Plasma Cell / drug therapy
  • Leukemia, Plasma Cell / pathology
  • Leukemia, Plasma Cell / surgery
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / surgery
  • Oligopeptides / therapeutic use
  • Proteasome Inhibitors / therapeutic use
  • Recurrence
  • Salvage Therapy*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Oligopeptides
  • Proteasome Inhibitors
  • carfilzomib