A Prospective Phase II Trial of Lenalidomide and Dexamethasone (Len-Dex) in POEMS Syndrome

Jaccard, Arnaud; Danielou-Lazareth, A.; Karlin, Lionel; Choquet, Sylvain; Frenzel, Laurent; Garderet, Laurent; Dib, Mamoun; Galicier, Lionel; Tournilhac, O.; Belhadj, Karim; Moreau, P.; Decaux, Olivier; Benboubker, Lotfi; Slama, Borhane; Bonnotte, B.; Hébraud, Benjamin; Cogné, Michel; Musset, L.; Fermand, Jean Paul

doi:10.1016/j.clml.2015.07.197

Cited by 6 publications

(6 citation statements)

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“…Detailed clinical features and laboratory information were collected at the time of diagnosis, as described previously . Briefly, overall neuropathy limitation scale (ONLS) conducted by the same operator was used to assess neurologic disability, as other clinical studies of POEMS syndrome . Laboratory studies included serum VEGF, protein electrophoresis, serum and urine immunofixation electrophoresis, and bone marrow examinations.…”

Section: Methodsmentioning

confidence: 99%

“…However, 45% developed lenalidomide‐related grade 3 or 4 adverse events, which were predominantly hematologic. The same regime has also been evaluated in a prospective phase II study, in which Jaccard and colleagues treated 27 newly diagnosed or relapsing patients. Although the follow‐up is short, evaluable patients had rapid VEGF response and neurological improvement, no patient has died.…”

Section: Introductionmentioning

confidence: 99%

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A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

Huang

Cai

et al. 2018

American J Hematol

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Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare plasma dyscrasia without standard treatment. This phase II prospective trial evaluates the safety and response of 12 cycles of low dose lenalidomide (10 mg) plus dexamethasone (Rdex) in patients with newly diagnosed POEMS syndrome. Forty-one patients (28 men) were enrolled and the median age at diagnosis was 49 years (range, 21-70 years). Twenty-one patients (46%) achieved complete hematologic response and the neurologic response rate was 95%. The median serum vascular endothelial growth factor (VEGF) declined from 5155 pg/mL (range, 534-14 328 pg/mL) to 832 pg/mL (95-6254 pg/mL) after therapy. The overall VEGF response rate was 83%, and the median time to response was 2 months, with a mean VEGF reduction of 43% at the first month. In terms of clinical response, Rdex substantially relieved extravascular volume overload, organomegaly, and pulmonary hypertension. No treatment-related deaths occurred and no patients suffered from lenalidomide-related grade 3 or above adverse events. After a median follow-up of 34 months, median overall survival (OS) and progression-free survival (PFS) were not reached, with an estimated 3-year OS and PFS of 90% and 75%, respectively. In conclusion, Rdex was active with high hematologic, VEGF and organ response rate and well tolerated for patients with newly diagnosed POEMS syndrome. This trial was registered at www.clinicaltrials.gov as #NCT01816620.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

Huang

Cai

et al. 2018

American J Hematol

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“…Thalidomide in combination with dexamethasone has also shown to produce responses in terms of VEGF, peripheral neuropathy, and extravascular volume overload, but hematologic responses have not been reported . Enthusiasm for this therapy should be tempered by the risk of peripheral neuropathy induced by this drug.…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

POEMS Syndrome: 2019 Update on diagnosis, risk‐stratification, and management

Dispenzieri

2019

American J Hematol

225

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Disease Overview: Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria. Risk Stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR. Risk-Adapted Therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

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“…The French have reported in abstract form their results of a Phase 2 study of lenalidomide and dexamethasone for 2 cycles as neoadjuvant therapy preceding radiation or high dose therapy or as primary therapy as 9 cycles followed by 12 cycles of single agent lenalidomide . They have treated 27 patients: 10 preradiation therapy, 8 pre‐ASCT, and 9 as primary therapy.…”

Section: Management Of Poems Syndrome With Disseminated Bone Marrow Imentioning

confidence: 99%

POEMSsyndrome: 2017 Update on diagnosis, risk stratification, and management

2017

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Disease Overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.Diagnosis: The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.Risk Stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy Risk-Adapted Therapy: For those patients with a dominant sclerotic plasmacytoma, first-line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3-6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low-dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti-VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

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A Prospective Phase II Trial of Lenalidomide and Dexamethasone (Len-Dex) in POEMS Syndrome

Cited by 6 publications

References 0 publications

A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

POEMS Syndrome: 2019 Update on diagnosis, risk‐stratification, and management

POEMSsyndrome: 2017 Update on diagnosis, risk stratification, and management

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