Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma

The Rockefeller University, New York, New York, United States
British Journal of Haematology (Impact Factor: 4.71). 02/2006; 132(2):155-61. DOI: 10.1111/j.1365-2141.2005.05848.x
Source: PubMed


Among the drug combinations designed for the initial treatment of multiple myeloma, none has been unequivocally shown to be superior. However, a regimen leading to a high response rate and a low incidence of adverse events is highly desirable. We report the results of a phase II clinical trial involving 45 patients with Durie-Salmon stage II and III multiple myeloma. Doxorubicin and dexamethasone were given for 2 or 3 months followed by thalidomide and dexamethasone for 2 months (AD-TD regimen) with prophylactic antibiotics and daily aspirin (81 mg/d). Among the 42 patients whose response could be assessed, 38 responded to therapy (90.5%). The intent-to-treat response rate was 84.4% with seven complete responses (CR 15.5%), nine near complete responses (nCR 20.0%), and 22 partial responses (PR 48.9%). Two patients had stable disease (4.4%), and two progression of disease (4.4%). Normalization of the free light chain ratio after one or two cycles of treatment was highly predictive of achievement of CR or nCR. Patients tolerated the treatment well although five patients developed thromboembolic complications (11%). AD-TD administered with low dose aspirin for deep vein thrombosis prophylaxis was well tolerated and yielded a high response rate with minimal treatment-related morbidity.

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Available from: Adam D Cohen, Mar 24, 2015
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    • "Following chemotherapy, changes in serum FLC concentrations and intact immunoglobulins occur in parallel but FLC levels usually fall much more rapidly, particularly with IgG myelomas given the longer half-life compared to IgA (Bradwell et al, 2003; Mead et al, 2004; Pratt et al, 2006). Earlier disease assessment may be of value in detecting poorly responding patients who need alternative forms of therapy, in identifying earlier patients who have had a maximal response or predicting patients who will achieve a complete response (Hassoun et al, 2006). Conversely the most rapidly responding patients may have a worse outcome (van Rhee et al, 2007). "
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    ABSTRACT: Over the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2-4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100-150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non-secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non-secretory and oligo-secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of lambda and kappa free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.
    Full-text · Article · Jun 2008 · British Journal of Haematology
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    • "Serum FLC ratios (kappa/lambda) lying outside the normal range (0.26 to 1.65, [6]) indicate monoclonal FLC production arising as a result of clonal expansion [6,7]. Serum FLC levels and ratios are now routinely measured to diagnose and monitor disease progression and response to therapy in light chain multiple myeloma [8], nonsecretory myeloma [9], intact immunoglobulin myeloma [10,11] primary AL amyloidosis [12], and to risk stratify patients with monoclonal gammopathy of unknown significance (MGUS) [13]. B-cell Non-Hodgkin's Lymphomas likewise exhibit a light chain restriction, so that measuring free light chain concentrations in CSF could particularly aid the diagnosis of LM. "
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    ABSTRACT: Lymphomatous meningitis (LM) represents a severe complication of malignant lymphomas. While clinical suspicion is raised by symptoms ranging from mild disturbances of sensation to severe pain or impaired consciousness, the definite diagnosis of LM is often difficult to obtain. Since B-cell lymphomas are clonally restricted to express either kappa or lambda immunoglobulin light chain, we hypothesised that analysis of free light chain (FLC) ratios might facilitate the diagnosis of LM. Kappa and lambda FLC were measured using a novel nephelometric assay in cerebrospinal fluid (CSF) and serum from 17 patients. 5/17 suffered from LM as demonstrated by cytology, immunocytology, and/or imaging procedures. Measurement of FLC concentrations in CSF was achieved for all 17 patients. FLC levels in CSF were lower than serum FLC levels in samples for the same patient obtained at the same time (p < 0.01). CSF and serum FLC concentrations correlated weakly in all patients irrespective of LM status. Significantly more patients with cytopathologically and immunohistochemically proven LM displayed abnormal kappa/lambda FLC ratios in CSF compared to individuals with no LM (p < 0.01). This is the first report demonstrating that a significant proportion of LM patients display an abnormal kappa/lambda FLC ratio in the CSF.
    Full-text · Article · Feb 2007 · BMC Cancer
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    • "The high response rate and good tolerability of doxorubicin/ dexamethasone followed by thalidomide/dexamethasone with prophylactic antibiotics and 81 mg aspirin a day in the recent trial in stage II/III myeloma (Hassoun et al, 2006) may provide a welcome option for initial treatment. However, since aspirin and other cyclooxygenase inhibitors have a long documented history of increasing the circulating levels of tumour necrosis factor-alpha (TNF-a) (Kast, 2000), a note of caution is warranted. "

    Preview · Article · May 2006 · British Journal of Haematology
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