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Blood, 15 January 2007, Vol. 109, No. 2, pp. 391-392. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schechter, G. P. Search for Related Content PubMed Articles by Schechter, G. P. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this? Next Article  CLINICAL TRIALS AND OBSERVATIONS Comment on Dispenzieri et al, page 465, comment on Sanchorawala et al, page 492, and comment on Wechalekar et al, page 457 A triple on AL amyloidosis, waiting for a home run Geraldine P. Schechter WASHINGTON VA MEDICAL CENTER; GEORGE WASHINGTON UNIVERSITY New therapies for amyloid light-chain (AL) amyloidosis are sorely needed. This issue of Blood brings encouraging results from 3 studies of new and old antimyeloma treatments for this lethal multisystemic disorder. Dispenzieri and colleagues and Sanchorawala and colleagues studied lenalidomide with and without dexamethasone, and Wechalekar and colleagues combined cyclophosphamide, dexamethasone, and thalidomide in their larger study. Amyloid light-chain (AL) amyloidosis results from the deposition of light chains prone to fibril formation produced by "dangerous small B-cell clones."1(p2520) For the last 2 decades, treatment approaches have attempted to reduce the clones by using antimyeloma regimens, relying on the hypothesis that amyloid fibril deposition into various organs is a dynamic process and will be reduced once production of amyloidogenic light chains is eliminated. Unfortunately, clonal and organ response rates to standard antimyeloma therapy have been low. The best response rates occur following high-dose chemotherapy and autologous stem cell transplantation, but only a minority benefit due to high mortality and morbidity rates.2,3 The 2 phase 2 studies of 22 and 24 patients of the recently FDA-approved, but costly IMiD, lenalidomide, by Dispenzieri and colleagues and Sanchorawala and colleagues are very similar. In both studies, the usual myeloma dose was too toxic for amyloidosis patients, resulting in high early dropout rates and few responses. Addition of high-dose dexamethasone to reduced doses of lenalidomide resulted in good overall hematologic (clonal) response rates of 43% and 47%, in Dispenzieri et al and Sanchorawala et al, respectively. Organ responses, however, occurred in only 23% and 17% of the patients, mainly after clonal responses. Toxicity continued to be a problem, with significant adverse effects occurring in up to 86% of patients, including myelosuppression, fatigue, infections, rashes, and thromboembolic events. Four deaths occurred in each study, apparently due to amyloid progression rather than toxicity. The study by Wechalekar and colleagues is a larger retrospective study of 75 patients treated with a risk-adapted regimen of cyclophosphamide, dexamethasone, and thalidomide and followed at the National Amyloidosis Centre, United Kingdom, with 123I–serum amyloid P component (SAP) scintigraphy as well as the usual light chain measurements. These patients were considered ineligible for high-dose chemotherapy by British guidelines.4 The 74% clonal response rate was impressive for a nontransplantation regimen, but organ responses lagged behind at 27%. 123I-SAP scans showed regression of liver deposits in responding patients (see the figure) but less often, decreases in kidney deposits. Fewer patients had significant adverse effects; treatment-related mortality occurred in 4%. However, the patients represented only 4.8% of those seen at the Centre over 5 years, raising the question of possible selection bias, although patient characteristics were similar to those described in the other 2 studies, except that severe autonomic or peripheral neuropathy patients were excluded. View larger version (128K): [in this window] [in a new window]   Serial 123I-labeled anterior whole-body SAP scintigraphy. See the complete figure in the article beginning on page 457.   These 3 studies' clonal response rates in these seriously ill patients and the durability of the responses in the longer United Kingdom study are encouraging. However, the poor organ response rates in all 3 studies point to the clear need for new treatment modalities that can mobilize amyloid out of the tissues more efficiently while the clones are being reduced with less toxic (and less expensive) drugs. Footnotes Conflict-of-interest disclosure: The authors declare no competing financial interests. References Merlini G and Stone M. Dangerous small B-cell clones. Blood 2006; 108:2520–2530.[Abstract/Free Full Text] Skinner M, Sanchorawala V, Seldin DC, et al. High dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis, an 8-year study. Ann Intern Med 2004; 140:85–90.[Abstract/Free Full Text] Vesole DH, Perez WS, Akasheh M, et al. High-dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis: a Center for International Blood and Marrow Transplant Research Study. Mayo Clin Proc 2006; 81:880–888.[Medline] [Order article via Infotrieve] Guidelines on the diagnosis and management of AL amyloidosis. Br J Haematol 2004; 125:681–700.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial Vaishali Sanchorawala, Daniel G. Wright, Michael Rosenzweig, Kathleen T. Finn, Salli Fennessey, Jerome B. Zeldis, Martha Skinner, and David C. Seldin Blood 2007 109: 492-496. [Abstract] [Full Text] [PDF] The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis Angela Dispenzieri, Martha Q. Lacy, Steven R. Zeldenrust, Suzanne R. Hayman, Shaji K. Kumar, Susan M. Geyer, John A. Lust, Jacob B. Allred, Thomas E. Witzig, S. Vincent Rajkumar, Philip R. Greipp, Stephen J. Russell, Brian Kabat, and Morie A. Gertz Blood 2007 109: 465-470. [Abstract] [Full Text] [PDF] Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis Ashutosh D. Wechalekar, Hugh J. B. Goodman, Helen J. Lachmann, Mark Offer, Philip N. Hawkins, and Julian D. Gillmore Blood 2007 109: 457-464. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schechter, G. P. Search for Related Content PubMed Articles by Schechter, G. P. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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