Dexamethasone Based Therapies

In 1997, Dhodapkar et al. first described the clinical activity of dexamethasone (DEX) in AL amyloidosis.44 Several studies have since confirmed this finding.45-48 In a recent US Intergroup trial, 93 patients were treated with induction therapy with pulsed DEX, followed by DEX and alpha interferon as maintenance.37 Complete hematologic remissions (CHR) were observed in 24 %. Improvement in AL-related organ function was seen in 45% of patients. Overall survival in the entire cohort was 31 months. The presence of congestive heart failure (CHF) and elevated serum p-2 microglobulin were dominant adverse prognostic factors. Patients with both of these features do poorly with DEX and should not be treated with this regimen. DEX has also been administered as a part of regimens that include mel-phalan49 or doxorubicin-vincristine,45 with promising results. However, whether the addition of these agents adds significantly to DEX alone remains unclear. The use of melphalan may have an impact on stem cell collection in patients eligible for stem cell transplantation, and should therefore be avoided before stem cell collection.

The tolerance to DEX in AL amyloid is lower than that in myeloma. This has prompted investigators to use reduced doses at the initiation of therapy, with dose escalation based on tolerance. Controlled studies are needed to compare DEX-based regimens to MP and to stem cell transplantation. Recent studies have identified the activity of several new drugs, such as thalidomide and bortezomib in combination with DEX in myeloma.5051 These regimens are currently undergoing active evaluation in the therapy of AL amyloidosis.

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