Thalidomide in multiple myeloma: lack of response of soft‐tissue plasmacytomas

Bladé, Joan; Perales, Marı́a; Rosiñol, Laura; Tuset, Montserrat; Montoto, Silvia; Esteve, Jordi; Cobo, Francesc; Villela, Luís; Rafel, Montserrat; Nomdedeu, Benet; Montserrat, Emili

doi:10.1046/j.1365-2141.2001.02765.x

Cited by 79 publications

(59 citation statements)

References 13 publications

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“…A possible association has been reported between the presence of extramedullary myelomatous lesions and a poor response to thalidomide, 45,46 including cases with extramedullary progression, although bone marrow response. 47 However, other authors have highlighted responses in this case to thalidomide.…”

Section: Discussionmentioning

confidence: 99%

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

García‐Sanz¹,

González‐Porras²,

Hernández³

et al. 2004

Leukemia

140

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We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/ day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intentionto-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR þ PR þ MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with b 2 microglobulin p4 mg/dl, platelets 480 Â 10 9 /l and nonrefractory disease. Regarding survival, low b 2 microglobulin (p4 mg/dl), age (p65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with b 2 microglobulin p4 mg/dl and p65 years.

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Section: Discussionmentioning

confidence: 99%

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

García‐Sanz¹,

González‐Porras²,

Hernández³

et al. 2004

Leukemia

140

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“…15 Since then several studies of thalidomide and other novel agents have provided an early estimate of the impact of these therapies, given previous data demonstrating a median survival of 17 months from the time of first relapse of myeloma. [16][17][18][19][20][21] Phase III randomized trials of bortezomib and lenalidomide have demonstrated a survival benefit in patients with relapsed disease. 22,23 In the Assessment of Proteasome Inhibition for Extending Remission (APEX) trial, bortezomib therapy improved 1-year survival from 66% to 80% compared with dexamethasone alone.…”

Section: Discussionmentioning

confidence: 99%

Improved survival in multiple myeloma and the impact of novel therapies

Kumar

Rajkumar

Dispenzieri

et al. 2008

Blood

2,050

1,481

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Treatments for myeloma have expanded in the last decade, but it is not clear if the introduction of novel therapies and the increased use of high-dose therapy have translated into better outcome for patients with myeloma. We examined the outcome of 2 groups of patients seen at a single institution, one from time of diagnosis and the other from the time of relapse, to examine the survival trends over time. Among 387 patients relapsing after stemcell transplantation, a clear improvement in overall survival from the time of relapse was seen, with those relapsing after 2000 having a median overall survival of 23.9 versus 11.8 months (P < .001) for those who relapsed prior to this date. This improvement was independent of other prognostic factors. Patients treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 vs 14.8 months; P < .001). In a larger group of 2981 patients with newly diagnosed myeloma, those diagnosed in the last decade had a 50% improvement in overall survival (44.8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis. IntroductionMultiple myeloma (MM), a neoplasm of plasma cells, affects 1 to 5 per 100 000 individuals each year worldwide with a higher incidence in the West. 1 It is the second most common hematologic malignancy in the United States, and it is estimated that there will be 19 900 new diagnoses and 10 790 deaths due to myeloma in 2007. 2 The median survival of patients with MM was less than a year before introduction of alkylating agents, and the introduction of melphalan in the 1960s resulted in improved survival. 3,4 A timeline of major therapeutic advances in multiple myeloma is outlined in Table 1. In the 1980s, introduction of high-dose chemotherapy and stem-cell rescue (ASCT) was introduced, and randomized trials since have demonstrated a survival advantage for this modality compared with conventional chemotherapy (CCT). [5][6][7] The introduction of thalidomide represented a major milestone in the treatment of myeloma, and the subsequent availability of its analog lenalidomide and the proteasome inhibitor bortezomib have expanded the therapeutic armamentarium for myeloma. [8][9][10][11][12] Incorporation of these novel agents has resulted in a paradigm shift in the treatment of myeloma, with their use earlier in the disease course. 13 While the new drugs have allowed successful salvage of relapsed disease, it is not clear if the survival of patients has improved during the last few years. We examined patients seen at our institution over a 36-year period to determine whether there has been an improvement in survival of myeloma patients seen during this time period. MethodsWe examined 2 cohorts of patients seen at Mayo Clinic with a diagnosis of MM. The first cohort consisted of 387 patients who were examined for potential improvement in survival following first relapse after ASCT. These patients we...

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“…Hence, we have seen a similar lack of response to thalidomide in the plasmacytomas but a marked improvement in serum/urinary protein levels, as found in two of the patients described in the series of Blade Â et al (2000). It is interesting to speculate why there should be such a significant difference in response when presumably thalidomide can reach these vascular areas easily, and possibly it may imply a difference in the malignant cell itself.…”

Section: Lack Of Response To Thalidomide In Plasmacytomasmentioning

confidence: 66%

“…We read with interest the short report by Blade Â et al (2000) regarding the lack of response to thalidomide in five patients with extramedullary plasmacytomas. Two of the patients showed reduction in paraprotein/light-chain excretion but with progressive extraosseous plasmacytomas, whereas the remaining three had progression of their plasmacytomas with no decrease in the paraprotein.…”

Section: Lack Of Response To Thalidomide In Plasmacytomasmentioning

confidence: 93%

The spherocytic haemolytic anaemias

Bain¹

2001

Br J Haematol

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Thalidomide in multiple myeloma: lack of response of soft‐tissue plasmacytomas

Cited by 79 publications

References 13 publications

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

Improved survival in multiple myeloma and the impact of novel therapies

The spherocytic haemolytic anaemias

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