Correspondence

Bortezomib in Multiple Myeloma

N Engl J Med 2003; 349:1287-1288September 25, 2003

Article

To the Editor:

Proteasome inhibition is an interesting approach to the treatment of multiple myeloma, but the results of the study by Richardson et al. (June 26 issue)1 are difficult to evaluate. Although the authors claim an overall response rate of 35 percent, more than two thirds of these responses were either “partial” or “minimal” — terms the authors failed to define. They mention that some patients actually had an increase in the levels of monoclonal immunoglobulin (but do not include this category in Table 2 of their article). It would also be helpful to know what the investigators mean by “disease progression,” since the chief advantage of bortezomib over conventional therapy appears to be the duration of the response.

James D. Faix, M.D.
Stanford University School of Medicine, Stanford, CA 94305-5627
jim.faix@stanford.edu

1 References

1. 1

   Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348:2609-2617
   Full Text | Web of Science | Medline

To the Editor:

In their study of bortezomib, Richardson et al. report a 31 percent incidence of peripheral neuropathy. Were peripheral-nerve biopsy specimens from several affected patients examined for the deposition of paraprotein, such as beta-amyloid?

Arnold I. Meisler, M.D.
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232
meislerai@msx.upmc.edu

Author/Editor Response

Responses in our study were assessed according to the European Group for Blood and Marrow Transplantation (EBMT) criteria.1 A partial response was defined as a decrease in the level of monoclonal protein of more than 50 percent in serum and more than 90 percent in urine and a minimal response as a decrease of more than 25 percent and more than 50 percent, respectively, on two determinations six weeks apart, with stable bone radiographs and normal serum calcium levels. Fifty-nine percent of the patients had either stabilization of their paraprotein level or a response (Table 2 of our article). Therefore, 41 percent of the patients were considered not to have had a response; they either had progression or left the study before evaluation of the response. Disease progression in our study was defined according to EBMT criteria as an increase in the monoclonal protein level of more than 25 percent or the development of hypercalcemia, new bone disease, or plasmacytomas.

In response to Dr. Meisler: nerve biopsies were not performed in the patients enrolled in our trial. However, neurologic evaluation was performed at base line and at repeated intervals during treatment. Moreover, a subgroup of patients also underwent nerve-conduction studies and quantitative sensory testing. The clinical and electrophysiological characteristics of the neuropathy were consistent with the presence of a length-dependent, sensory, axonal polyneuropathy with predominant small-fiber involvement.

Paul G. Richardson, M.D.
Dana–Farber Cancer Institute, Boston, MA 02115
paul_richardson@dfci.harvard.edu

David P. Schenkein, M.D.
Millennium Pharmaceuticals, Cambridge, MA 02139

Kenneth C. Anderson, M.D.
Dana–Farber Cancer Institute, Boston, MA 02115

1 References

1. 1

   Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol 1998;102:1115-1123
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Roberto R Rosato, Steven Grant. (2004) Histone deacetylase inhibitors in clinical development. Expert Opinion on Investigational Drugs 13:1, 21-38
   CrossRef