Low-Dose Thalidomide and Dexamethasone Improves Survival in Advanced Multiple Myeloma

Reviewer: Ryan Smith, MD
Last Modified: December 10, 2002

Presenter: Antonio Palumbo
Presenter's Affiliation: Divisione di Ematologia dell'Unversita di Torino
Type of Session: Scientific


    The standard treatment for multiple myeloma (MM)for decades had been melphalan and prednisone. High dose chemotherapy and bone marrow transplant has imroved outcomes, but relapses continue to occur and many patients cannot tolerate these aggressive regimens. Therefore, newer regimens such as thalidomide and dexamethasone have been evaluated as alternative treatments. This study reports on outcome and toxicity of this regimen, comparing it to more classical combination chemotherapy.

Materials and Methods

  • 120 patients with relapsed or refractory MM after chemotherapy were treated with thalidomide 100 mg/d plus dexamethasone 40 mg/d on days 1-4 of each month.
  • Outcome in the thalidomide group was compared to a group of 120 matched controls with relapsed/refractory MM treated with further chemotherapy.
  • Matching prognostic factors included B2Microglobulin levels and Durie and Salmon clinical stage
  • 50% of patients were enrolled after failing one line of chemotherapy, 25% after failing 2 lines of chemotherapy, and 25% after failing 3 lines of chemotherapy.
  • Median follow up was 18 months for the thalidomide-dexamethasone group and 22 months for the chemotherapy group
  • Data is reported from time of start of therapy


  • In the thalidomide group, 38% are alive and in remission and 62% of patients relapsed. In those patients that relapsed, 55% died from disease progression.
  • In the matched chemotherapy group, 13% are alive and in remission and 87% have relapsed. In those patients that have relapsed, 81% died of disease progression.
  • Median progression free survival (PFS) was 13 months in the thalidomide group compared to 11 months in the chemotherapy group.
  • Overall survival was 27 months in the thalidomide group vs. 19 months in the chemotherapy group (P<.05)
  • When analyzing data in terms of those patients being treated for their first relapse, PFS was 18 mo vs. 11 months (p<.03) and overall survival was 30 months vs. 21 months (p<.01), both in favor of the thalidomide group.
  • Thalidomide-dexamthasone treatment had toxicity associated with it: 32% polyneuropathy, 17% constipation, 13% sedation, 7% confusion, 2% DVT
  • Thalidomide-dexamethasone treatment was discontinued in 18% of patients, mainly due to neuropathy.

Author's Conclusions

  • Resonse, PFS, and overall survival is better with thalidomide-dexamethasone when compared to combination chemotherapy
  • Toxicity is a concern with thalidomide, with polyneuropathy being the major long-term toxicity. This leads to the discontinuation of treatment in a significant number of patients.

Clinical/Scientific Implications

    The typical disease course for MM is that of many relapses with subsequent treatments with chemotherapy, usually each having a shorter and shorter durability of response. Hence, newer combinations of chemotherapy are constantly being studied for efficacy in the treatment of MM. One of the most encouraging of these is thalidomide. This study demonstrates the effecacy of thalidomide-dexamethasone in relapsed or refractory MM. The use of this regimen would be especially beneficial, since its bone marrow toxicity is minimal. Given that patients have already received at least one regimen (and in many cases 2-3 regimens) of chemotherapy, any sparing of bone marrow is obviously helpful, though thalidomide has a toxicity profile of its own, as shown. However, it should be pointed out that this is not a randomized study. Although an effort was made to match controls on known prognostic factors, selection biases and differences in patient characteristics are bound to exist. Therefore, though thalidomide's effect on response, disease progression, and survival appears to be efficacious, this is not a direct comparison with traditional combination chemotherapy.

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