Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide? A retrospective analysis of data from the GIMEMA, Nordic and Turkish myeloma study groups

Acta Haematol. 2015;133(4):372-380. doi: 10.1159/000370023. Epub 2015 Mar 24.

Abstract

Background/aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown.

Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH.

Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH.

Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Thalidomide / therapeutic use*
  • Treatment Outcome
  • Turkey

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Heparin, Low-Molecular-Weight
  • Thalidomide
  • Melphalan
  • Prednisone