lenalidomide (Revlimid) in POEMS

 

 

 

The 'cited' column indicates whether the article or abstract is mentioned in Dispenzieri's 2014 review ('D'), Li's 2013 review ('L'), or Zagouri's 2014 review of lenalidomide in POEMS ('Z').

If you have corrections or suggestions (or can figure out the numbers in the Zagouri study!), please let me know!

Harry A Ide
harryide6@gmail.com
last updated 6 August 2016

study # of patients follow-up (months) reason for using lenalidomide results cited notes
Yang 2016 35 12 months newly diagnosed significantly improved sexual function   changes in sexual function and VEGF were not correlated
Altinier 2016 4 ? ? M-protein absent in 3 patients; 1.75-1.20 g/L in the 4th; no response to therapy in 2, response in 2 (but recurrence 40 months later in 1)   3 other patients received other therapy
Yu 2015 1 2 weeks functional status ruled out auto developed recurrent epilepsy, renal failure, respiratory failure   patient refused treatment because of cost after 7 days of len-dex and died within a week. Castleman variant of POEMS (no evidence of plasma cell proliferative disorder)
Nakamura 2015 1 6 months poor functional status reduced VEGF 6 weeks after therapy started; significant neurological improvement 6 months after therapy started;  
Lestang 2015 8 median 26 months newly diagnosed neurological improvement in 7 patients (1 complete, 6 partial); all had reduced M proteins (3 complete, 3 partial); VEGF reduced in 5 (one progressed); other symptoms also improved (with rapid resolution of extra-vascular fluid overload)   see the abstract published as Lestang 2013. used the Dispenzieri 2003 criteria. at last follow-up, 3 patients still on therapy, 5 stopped (1 scheduled for auto, 1 progression, 1 grade 3 hematological toxicity, 2 stopped after good responses retained for 5 and 15 months)
Cai 2015 12 median 20 months relapsed or refractory POEMS -44% complete hematologic response; 77% some hematologic response

-67% neurological response

-VEGF response 91% (46% normalized VEGF)

-median time to improvement of extra-vascular fluid overload was 3 cycles (range 1-6); resolved in 92% by last follow-up

-one patient died after disease progression
  used 10 mg lenalidomide and 40 mg dex
Zagouri 2014 51 median 9 months [not summarized] -the analysis found 93.9% progression-free survival at 12 months

-neuropathy improved in 46/50 cases (92.0%) and stabilized in the other 4

-VEGF was reduced in all measured cases

-edema improved in 19/20 (95%) cases, and was stable in the remaining 1

-organomegaly improved in 20/23 (87%)

-skin changes improved in 14/19 (73.7%) and were stable in the other 5; platelets normalized in 12/13 (92.3%); pulmonary arterial hypertension and/or restrictive syndrome improved in 12/14 (85.7%).

-8 patients received auto's after lenalidomide; no problems with harvesting stem cells or with toxicity were reported.

-6 of 44 patients progressed (only two in first year), 1 while on lenalidomide and 5 after discontinuing lenalidomide.

-no deaths reported in follow-up period.

-clinically important adverse effects are mainly manageable hematological toxicity.
  -pooled analysis of 11 studies, with 4 new patients, with a total of 51 cases.
Ueda 2014 1 18 months (?) [patient initially refused treatment, and refused auto to consolidate therapy] -dramatic reduction of massive ascites (average drained 18 L/month!); it disappeared after 7 courses

-plasma VEGF normalized after 18 months
  -10 mg; reduced to 5 mg because of reduced renal function

-patient also reported in Yonemoto 2012
Chu 2014 1 41 months after failed treatment with IVIG, dex, rituximab cyclophosphamide adriamycin vincristine and prednisone, and plasmapheresis lambda light chain normalized after 4 cycles; m-protein reduced; symptoms improved   after 15 months of rev-dex changed to lenalidomide 5 mg daily (continued to improve)
Royer 2013 20 median 22 months (6-58) -4 newly diagnosed

-16 relapsed or progressed (after corticosteroids (5), IVIG (2), melphalan + prednisolone (5), bevacizumab (2), irradiation (3), 1-5 years after auto (8); only auto had shown any efficacy)
-19/20 responded

-improvement in neuropathy (16 of 20; 3 wheelchair- or bed-bound patients became able to walk), organomegaly (13 of 13), peripheral edema (14 of 15), pulmonary hyptertension (5 of 5), serum VEGF (17 of 17 (with one increasing while on therapy after initially improving), normalized in 10/17), skin changes (9 of 13, with stabilization in 4)

-PET scans improved in 5 of 9 evaluable patients, were stable in 2, and became negative in 2.

-only mild toxicity, primarily hematological

-4 patients relapsed; 3 responded (to auto (1), irradiation (1), restarted lenalidomide (1)); 1 progressed

-2 patients who responded to len-dex had autos (after 2 and 12 cycles); 2 had irradiation (after 7 and 9 cycles)
DZ -includes patients in Jaccard 2009. 25 mg (15), 15 mg (2), 10 mg (3), 1 without dexamethasone. median 9 cycles (2-22).

-18-FDG-PET/CT negative in one patient with a sclerotic bone lesion detected on standard x-rays and on CT.

-large-scale prospective phase II study begun: either 2 cycles of lenalidomide-dexamethasone before irradiation or auto, or 9 cycles followed by 12 cycles of reduced dose lenalidomide for patients not eligible for irradiation or auto.
Ohashi 2013 1 11 courses relapse 4 years after auto -M-protein resolved (on immunofixation)

-improved from total incapacity to standing with slight assistance
  -article in Japanese; from abstract
Lestang 2013 8 1 to 12 m first-line treatment -partial neurological response in 7, complete in 1

-m-protein resolved in 4 patients, reduced by 50% in 2, and unchanged in 2

-serum VEGF normalized in 2, reduced in 2

-1 relapse 5 months after the end of treatment; complete response by auto
  abstract only. see the article (with longer follow-up) published as Lestang 2015
Furuta 2012 1 ? not stated -edema and sensory neuropathy improved; VEGF decreased Z -article in Japanese; from abstract

-excluded from Zagouri because of language

-patient diagnosed with POEMS 4 years after Waldenström's macroglobulinemia
Tomás 2012 10 median 7.5 cycles (6-18) salvage (after failure of chemotherapy in 4, rituximab in 1, immunoglobulins in 6) -5 of the patients had auto's after lenalidomide treatment

-clinical improvement in all

-neuropathy resolved in 4, significantly improved in the rest (apparently before the auto in the patients who received an auto later)

-of the 7 patients wheelchair or bed-bound, 3 patients became able to walk with assistance, and the others could walk indendently

-M-protein resolved (on immunofixation) in 5 patients

-therapy was transiently held in 2 patients because of respiratory infections
LZ -25 mg in 7 patients; 15 mg in 2; lenalidomide alone at 25 mg in 1
Briani 2012 3 ? not stated; 2 previously treated with steroids with no pachymeningeal improvement -VEGF resolved at 3 months

-Castleman's improved in 1 patient (after 5 cycles)

-strength and sensory neuropathy improved (after 3 cycles in 2 patients, 6 months in 1)

-stable neuropathy limitations

-dramatic MRI improvement of pachymeningeal involvement
LZ -patients with pachymeningeal involvement

-25 mg
Vannata 2012 1 19 months after relapse relapse 6 years after auto; repeat auto not possible because of poor performance status (ECOG 4) -ascites and dyspnea resolved (after 1 cycle)

-splenomegaly resolved (after 4 cycles)

-M-protein resolved (after 6 cycles)

-plasma VEGF normal after 8 cycles

-neuropathy improved gradually (could walk with support after 6 cycles, independently after 10)

-bone lesion with persistent FDG-avidity irradiated after 10th cycle

-lenalidomide restarted 3 months later because of increased plasma VEGF
LZ -25 mg
Adam 2012 1 4 cycles -insufficient efficacy of prior treatments

-4th line treatment, after (1) cyclophosphamide adriamycine dexamethasone, (2) auto, (3) thalidomide (not well tolerated)
no remission [no other discussion in the abstract] Z -article in Czech; from abstract
Matsuura 2012 1 ? initial treatment, before auto -significantly decreased serum VEGF

-M-protein resolved (after 2 cycles)

-no significant adverse effects
Z -article in Japanese; from abstract

-excluded from Zagouri because of language
Suyani 2011 1 9 cycles + 1 year not stated -significant improvement in neuropathy (after 4 cycles)

-papilledema and M-protein resolved (after 6 cycles)

-only toxicity grade II neutropenia and grade 1 anemia
L -25 mg (with cyclophosphamide and prednisolone)

-excluded from Zagouri because diagnosis was 'incomplete POEMS syndrome' because she had no sclerotic lesions, and no clonal plasma cells in bone marrow (p.200)

-This is confusing, since the article mentions a serum M-protein, which is enough to meet the 'monoclonal plasma cell proliferative disorder' criterion.

-But the evidence doesn't prove the patient meets Dispenzieri's current criteria; she had the two mandatory major criteria, and multiple minor criteria (organomegaly, endocrinopathy, skin changes, papilledema), but may not meet the other mandatory criterion, since she had no sclerotic bone lesions (apparently only on skeletal survey), VEGF wasn't measured, and while the article mentions 'mesenteric, paracaval and paraaortic lymph nodes with a maximum diameter of 2 cm' (p.200), it says nothing about Castleman disease]
Patel 2011 1
[of 5 receiving auto's in the study]
? treatment before auto -[describes responses to autos; can't identify individuals] L -presumably included in the 7 patients in Patel 2014, which says only that '[a]ll patients received systemic therapy prior to auto-HCT'
Nozza 2011 10 median 10 cycles (5 to 18) not stated, but all patients pretreated; 2 had transplants -neurological improvement evident after 3 cycles; NCS confirmed after 6 cycles

-all 5 evaluable patients improved clinically, with all disease manifestations improving

-lenalidomide was reduced in two patients; dexamethasone in 5

-3 patients discontinued:
1 withdrew consent
1 dropped out with progression after 4 cycles
1 died in cycle 1 of pulmonary infection)
Z -abstract only

-25 mg
Ramirez 2009 1 4 cycles not stated -neurological and respiratory improvement (after 4 cycles)

-decreased VEGF etc.
Z -25 mg
Sethi 2009 1 4 cycles not stated -marked clinical improvement

-neuropathy nearly resolved

-kappa-lambda ratio decreased to 1.71
LZ -25 mg
Patel 2008 1 10 cycles relapse after auto; performance status too poor for repeat auto -performance status improved (by 2nd cycle)

-splenamegaly improved

-ascites and encephalopathy resolved

-no longer required oxygen

-side effect: weight gain due to dexametasone (which was discontinued)

-"Lazarus response" (!)
Z -abstract only

-started at 10 mg; gradually increased to 25 mg
Kuehne 2008 1 6 months progression after corticosteroids, cyclophosphamide, azathioprine -free λ light chains normalized

-significant improvement in neuropathy (by 4th cycle)

-strength and fatigue (by 2nd cycle)

-side effects: transient mild liver enzyme elevation, constipation
Z -abstract only
Dispenzieri 2007 1 10 months performance status too poor for auto -neurological improvement by 3rd cycle

-substantially improved functional status, VEGF, IL-6, skin changes, anasarca

-some improvement in PFTs, hypergammaglobulinemia, testosterone
LDZ -15 mg, gradually increased to 25 mg

-9 cycles in 9 months

-auto planned to consolidate response
Adam 2012
Adam Z, Pour L, Krejcí M, Zahradová L, Szturz P, Koukalová R, Rehák Z, Nebeský T, Hájek R, Král Z, Mayer J. '[The effect of lenalidomide on rare blood disorders: Langerhans cell histiocytosis, multicentric Castleman disease, POEMS syndrome, Erdheim-Chester disease and angiomatosis].' Vnitr Lek 2012 Nov;58(11):856-66. [Article in Czech]
Altinier 2016
Altinier S, Proko K, Zaninotto M, Ciubotaru D, Seguso M, Varagnolo M, Lessi F, Briani C, Adami F, Plebani M. 'Free light chains and heavy/light chains in monitoring POEMS patients'. Clinical chemistry and laboratory medicine 2016 Jun 1;54(6):1065-71. doi: 10.1515/cclm-2015-0910.
Briani 2012
Briani C, Manara R, Lessi F, Citton V, Zambello R, Adami F. 'Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy.' Am J Hematol 2012 May;87(5):539-41. doi: 10.1002/ajh.23148. Epub 2012 Mar 3.
Cai 2015
Cai QQ, Wang C, Cao XX, Cai H, Zhou DB, Li J. 'Efficacy and safety of low dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome'. European Journal of Haematology European journal of haematology 2015 Oct; 95(4): 325-30.
Chu 2014
Chu BF, Shana'ah A, Hofmeister CC, Benson DM, Sell M, Tucker J, Pichiorri F, Efebera YA. 'Long-Term Therapy with Lenalidomide in a Patient with POEMS Syndrome'. Eur J Case Rep Intern Med. 2014;1. pii: 2014_000093.
Dispenzieri 2007
Dispenzieri A; Klein CJ; Mauermann ML. 'Lenalidomide therapy in a patient with POEMS syndrome. Blood 2007 Aug 1; 110(3): 1075-6
Furuta 2012
Furuta N, Tashiro Y, Ikeda M, Fujita Y, Okamoto K. '[A case of POEMS syndrome associated with Waldenström's macroglobulinemia and treated with lenalidomide].' Rinsho Shinkeigaku 2012;52(3):186-9. [Article in Japanese]
Jaccard 2009
Jaccard A, Abraham J, Recher C, et al. 'Lenalidomide therapy in nine patients with POEMS syndrome.' ASH Annu Meet Abstr 2009;114:3872.
Kuehne 2008
Kuehne R, Goede J, Benz R, et al. 'Immune modulatory drugs in POEMS syndrome'. Onkologie 2008;31(Suppl.4):Abstract P538.'
Lestang 2013
Lestang E, Caristan A, Graveleau J, Masseau A, Néel A, Connault J, Godmer P, Maisonneuve H, Blin N, Touzeau C, Moreau P, Hamidou M. 'Lénalidomide en première ligne dan le traitement du POEMS syndrome. Á propos de 8 observations'. La Revue de Médecine Interne 34 supplement 2 (Dec 2013) A30.
Lestang 2015
Lestang E, Caristan A, Néel A, Graveleau J, Duhamel E, Masseau A, Connault J, Maisonneuve H, Le Gouill S, Blin N, Touzeau C, Moreau P, Hamidou M. 'Lenalidomide as frontline therapy in polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome: a retrospective case series of eight patients'. Leukemia and lymphoma 2015 Jun;56(6):1895-6. doi: 10.3109/10428194.2014.974595. Epub 2015 Jan 21.s
Matsuura 2012
Matsuura S, Ogusa E, Taguchi J, Imai N, Fujita H, Tomita N, Ishigatsubo Y, Fujisawa S. '[POEMS syndrome treated with lenalidomide plus high-dose dexamethasone as a pre-transplant induction therapy].' Rinsho Ketsueki 2012 Dec;53(12):2025-8. [Article in Japanese]
Nakamura 2015
Nakamura K, Bechis MZ, Yee AJ, Dudzinski DM. 'Progressive Onset of Extracardiac and Myocardial Symptoms: Right Heart Failure and Cor Pulmonale in a Young Man With Debilitating Polyneuropathy and Monoclonal Gammopathy'. Circulation 2015 Jul 7;132(1):59-67. doi: 10.1161/CIRCULATIONAHA.115.016524.
Nozza 2011
Nozza A, Terenghi F, Mazza R, et al. 'Efficacy of lenalidomide in patients with POEMS syndrome: a pilot study'. Haematologica 2011;96(Suppl.3):Abstract C010.
Ohashi 2013
Ohashi K, Yokoyama A, Kagoo T, Hosoda T, Yamamoto R, Yoneda M, Kudo M, Boku S, Ueno H, Yano T. Rinsho Ketsueki 2013 Jul;54(7):670-4. '[Rapid improvement of fluid retention with lenalidomide plus low-dose dexamethasone for POEMS syndrome relapsed after autologous peripheral blood stem cell transplantation].' [Article in Japanese]
Patel 2008
Patel T, Moreno-Aspitia A. 'Alternative treatment for POEMS syndrome: a Lazarus response to lenalidomide'. Bood 2008;112(#11):Abstract 5205.
Patel 2011
Patel K, Orlowski RZ, Shah N, Bashir Q, Dinh YT, Rondon G, Giralt S, Champlin R, Qazilbash MH. 'Durable responses with autologous hematopoietic stem cell transplantation in patients with POEMS syndrome'. Blood (ASH Annual Meeting abstracts) 118 (2011) abstract 4522.
Ramirez 2009
Ramirez G, Campos A, Rosell A, et al. 'Patient suffering from POEMS syndrome treated with lenalidomide plus dexamethasone'. Haematologica 2009;94(Suppl.2):Abstract 1631.
Royer 2013
Royer B, Merlusca L, Abraham J, Musset L, Haroche J, Choquet S, Leleu X, Sebban C, Decaux O, Galicier L, Roussel M, Recher C, Banos A, Guichard I, Brisseau JM, Godmer P, Hermine O, Deplanque G, Facon T, Asli B, Leblond V, Fermand JP, Marolleau JP, Jaccard A. 'Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients.' Am J Hematol 2013 Mar;88(3):207-12. doi: 10.1002/ajh.23374. Epub 2013 Jan 18.
Sethi 2009
Sethi S, Tageja N, Arabi H, Penumetcha R. 'Lenalidomide therapy in a rare case of POEMS syndrome with kappa restriction.' South Med J 2009 Oct;102(10):1092-3. doi: 10.1097/SMJ.0b013e3181b2f7d8.
Suyani 2011
Suyani E, Yagci M, Sucak GT. 'Complete remission with a combination of lenalidomide, cyclophosphamide and prednisolone in a patient with incomplete POEMS syndrome.' Acta Haematol 2011;126(4):199-201. doi: 10.1159/000329896. Epub 2011 Aug 18.
Tomás 2012
Tomás JF, Giraldo P, Lecumberri R, Nistal S. 'POEMS syndrome with severe neurological damage clinically recovered with lenalidomide.' Haematologica 2012 Feb;97(2):320-2. doi: 10.3324/haematol.2011.041897. Epub 2011 Nov 4.
Ueda 2014
Ueda S, Yonemoto S, Oka K, Fujii N, Nakata K, Matsunaga H, Kataoka S, Iwama Y, Narahara H, Yasunaga Y, Inui Y, Kawata S. 'Lenalidomide and Dexamethasone for a Patient of POEMS Syndrome Presenting with Massive Ascites.' Case Rep Hematol 2014;2014:818946. doi: 10.1155/2014/818946. Epub 2014 Feb 19.
Vannata 2012
Vannata B, Laurenti L, Chiusolo P, Sorà F, Balducci M, Sabatelli M, Luigetti M, Giannotta C, De Stefano V, Leone G, Sica S. 'Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem-cell transplantation.' Am J Hematol 2012 Jun;87(6):641-2. doi: 10.1002/ajh.23195. Epub 2012 Apr 10.
Yang 2016
Yang HY, Huang X, Cai Q, Wang C, Cao X, Zhou D, Li J. 'Improvement of sexual function in POEMS syndrome after combination therapy of Lenalidomide and dexamethasone'. Orphanet J Rare Dis. 2016 Jun 18;11(1):80. doi: 10.1186/s13023-016-0461-8.
Yu 2015
Yu H, Yao F, Li Y, Li J, Cui QC. 'Castleman disease variant of POEMS syndrome complicated with multiple cerebral infarction: a rare case report and review of literature'. International Journal of Clinical and Experimental Pathology 2015 Oct 1;8(10):13578-83.
Zagouri 2014
Zagouri F, Kastritis E, Gavriatopoulou M, Sergentanis TN, Psaltopoulou T, Terpos E, Dimopoulos MA. 'Lenalidomide in patients with POEMS syndrome: a systematic review and pooled analysis.' Leukemia and Lymphoma 55 #9 (Sep 2014) 2018-2023.

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