A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma

Cancer. 2015 Oct 15;121(20):3622-30. doi: 10.1002/cncr.29533. Epub 2015 Jul 6.

Abstract

Background: Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons.

Methods: The authors performed a single-institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD-PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients.

Results: Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD-PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent-to-transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression-free survival of 4.5 months (95% confidence interval, 3.6-5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1-11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression-free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001).

Conclusions: The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered.

Keywords: CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone); DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin); VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide); chemotherapy; multiple myeloma; salvage.

Publication types

  • Clinical Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Infusions, Parenteral
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Salvage Therapy / methods*
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Thalidomide
  • Vincristine
  • Bortezomib
  • Etoposide
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Cisplatin

Supplementary concepts

  • CVAD protocol
  • DCEP protocol