Correspondence

Thalidomide for Multiple Myeloma

N Engl J Med 2006; 354:2389-2390June 1, 2006

Article

To the Editor:

Barlogie et al. (March 9 issue)1 report an increased response rate of multiple myeloma to thalidomide plus high-dose chemotherapy and transplantation. However, there was no difference in overall survival between the group that received thalidomide from the beginning of the study and the control group, which received thalidomide only after relapse.

The fact that no increase in survival was observed may be particular to the protocol of Barlogie et al., in which high-dose chemotherapy is given concurrently with thalidomide. This design amplifies drug-related toxicity and favors the emergence of tumor and stromal elements that are resistant to thalidomide. We believe that high-dose chemotherapy should not be given concurrently with thalidomide.

Judah Folkman, M.D.
Michael S. Rogers, Ph.D.
Harvard Medical School, Boston, MA 02115
judah.folkman@childrens.harvard.edu

1 References

1. 1

   Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006;354:1021-1030
   Full Text | Web of Science | Medline

Author/Editor Response

The availability of RNA from CD138-selected plasma cells and of unseparated marrow biopsy specimens from paired baseline and relapse samples should enable us to identify, by gene-expression profiling, thalidomide-induced alterations in myeloma cells or the microenvironment1 as the basis for resistance to thalidomide. The failure of thalidomide plus dexamethasone2 or thalidomide plus melphalan and prednisone3 to improve survival, despite a high response rate, suggests that resistance to thalidomide is not unique to the combinations of intensive cytotoxic chemotherapy used in our trial.

Bart Barlogie, M.D., Ph.D.
John Shaughnessy, Ph.D.
Guido Tricot, M.D., Ph.D.
Myeloma Institute for Research and Therapy, Little Rock, AR 72205
barlogiebart@uams.edu

3 References

1. 1

   Zhan F, Huang Y, Van Hemert R, Stephens O, Barlogie B, Shaughnessy J Jr. The gene expression signatures (GEP) of whole bone marrow biopsies (Bx) from patients with multiple myeloma (MM) in remission reflect disease risk and therapy. Blood 2005;106:444a-444a
   CrossRef | Web of Science

2. 2

   Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006;24:431-436
   CrossRef | Web of Science | Medline

3. 3

   Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367:825-831
   CrossRef | Web of Science | Medline

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