Bortezomib as a treatment for POEMS

Bortezomib (Velcade) is a promising treatment for POEMS. These are the articles I've seen mentioning it. The "cited" column indicates whether the article was cited in the reviews by Li 2013 ('L') or Dispenzieri ('D').

I did not include Zeng 2013a or Li 2011, because they are in Chinese, with no abstract available. I did not include Yuan 2009, which mentions POEMS, but found no evidence of POEMS in their patient (diagnosed with multiple myeloma and MCD).

Please send me corrections, suggestions, and additions!

Harry Ide <harryide6@gmail.com>

--last revised 18 February 2018

study	cited	treatment	sequence in treatment	results	diagnosis	comments
He 2017	D	CyBorD	first	11-month median follow-up; 19/20 improved ONLS score at least 1 point with a median decrease from 5 to 3; 13/17 resolved increased VEGF, 2 improved; 7/17 complete hematologic response, 6 partial, and 4 stable, ascites/pleural effusion resolved in 10/10, pulmonary hypertension in 7/7, almost all skin problems improved	Dispenzieri 2007 criteria	reduced dose: bortezomib 1 mg/m^2 iv on days 1-4, cyclophosphamide 200 mg iv on days 1-4, dexamethasone 20 mg iv on days 1-4 and 8-11
Kim 2016	1	bor-dex	1st	notable clinical improvement; walking with walker [after auto]	Dispenzieri 2007	28 days of bor-dex followed by auto
Hiyama 2016		bor-dex	first	plasma and serum VEGF fell; GFR improved	Dispenzieri 2007 criteria	2 six-week cycles; auto planned; also had breast cancer and was treated with mastectomy and tamoxifen
Bourgeault 2015		?	after mel-pred, cyclophosphamide-dex, radiation	'severe pain and violaceous discoloration of limbs'	Dispenzieri 2003 criteria	discontinued after 3 doses; next treated successfully with lenalidomide
Creamer 2014		VCD	first	[no information]	Dispenzieri 2007 criteria	six cycles of VCD, with auto planned
Haider 2013		plasma exchange (for hyperviscosity), steroids, bortezomib, 'followed by rituximab'	first	skin lesions, peripheral neuropathy, bleeding diathesis, and diastolic dysfunction improved after 3 cycless	Dispenzieri 2007 criteria. both Waldenstrom's macroglobulinemia and POEMS
Zeng 2013	D	BorDex	first	peripheral neuropathy etc. improved dramatically (ONLS decreased to 0) after 4 cycles, with complete hematological response	Dispenzieri 2007 criteria	auto performed 8 months after diagnosis
Ishii 2013		BorDex	first (with 40 Gy radiation of a single skeletal lesion)	[before auto] partial response, heart failure improved, improved neuropathy, decreased fluid retention, decreased VEGF	met Dispenzieri 2007 criteria	general condition warranted systemic treatment. no bortezomib neuropathy
Warsame 2012	D L	CyBorD	after post-auto relapse, lenalidomide, dexamethasone	dramatic improvement in functional capacity, skin problems, anasarca, in-range VEGF and IGA; no significant adverse reactions	met Dispenzieri 2007 criteria [Dispenzieri is the senior author]
Li 2012	L	BorDex	first	renal failure reversed (11 days after first cycle); neuropathy significantly improved (ONLS decreased from 5 to 2); hematological and VEGF complete response (after 3 cycles)	met Dispenzieri 2007 criteria	received 4 cycles of BorDex, followed by 12 cycles of melphalan-dexamethasone (to avoid bortezomib-induced neuropathy); improvement persisted 14 months after therapy was discontinued
Wang 2011	L	bortezomib-thalidomide	after failure of cyclophosphamide-methylprednisolone	8 cycles. neuropathy resolved; extrascular volume overload improved dramatically. stable 2 years after treatment	met Dispenzieri 2007 criteria	not eligible for auto because of poor performance status
Patel 2011		BorDex	before auto		Dispenzieri-2003 criteria	abstract only. 2 patients, but no details
Ohguchi 2011	D L	bortezomib followed by bortezomib-thalidomide	after failure of dexamethasone, and then melphalan-prednisolone	after 2 cycles, dramatic improvement of extravascular volume overload and VEGF normalized; normal PET after 3 cycles. added thalidomide starting with sixth cycle (because of fluid and m-protein), with resolution of fluid overload and m-protein undetectable by immunofixation. neuropathy gradually improved	Dispenzieri 2007 criteria	not eligible for auto because of poor performance status. 8 cycles
Braun 2011		BorDex	first	clear improvement clinically (including reduced edema) and on EMG/NCS after 4 cycles	Dispenzieri 2007 criteria	4 cycles, with 4 further cycles planned
Sobas 2010	L	BorDex	after relapse following steroids, Rituximab, CHOP minus vincristine	improvement after 3 cycles	MCD-POEMS variant (Dispenzieri 2007 criteria, but no M-protein)	not eligible for auto because of poor performance status. six cycles total. "complete remission" for four years.
Kaygusuz 2010	D L	BorDex	after failure of dexamethasone monotherapy	after seven cycles, serum M-protein 'declined to normal range' (does that mean it resolved?), neuropathy symptoms improved dramatically, etc.	used 'POEMS' for diagnosis. unclear whether Dispenzieri 2007 criteria were met (A) peripheral neuropathy (B) m-protein (D) peripheral edema, skin changes, hepatomegaly, thrombocytosis, and endocrinopathy also low B 12 but (C) no evidence of skeletal lesions (article refers only to bone survey), VEGF wasn't obtained because of technical problems, and the only evidence presented of lymphadenopathy was that CT showed only enlarged nodes each less than 1 cm in diameter	not eligible for auto because of poor performance status, but (later) auto planned
Tang 2009	D L	VDD	after failure of VAD, CMP, AD	complete hematological and VEGF response after four cycles, with improved neuropathic symptoms, and still in complete remission 7 months later	Dispenzieri 2007 criteria.

Abbreviations

AD: doxorubicin, dexamethasone
auto: autologous stem cell transplant
BorDex: bortezomib, dexamethasone
CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone
CMP: cyclophosphamide, melphalan, predisone
CyBorD: cyclophosphamide, bortezomib, dexamethasone
MCD: multicentric Castleman disease
VAD: Vincristine, doxorubicin, dexamethasone
VCD: bortezomib cyclophosphamide dexamethasone
VDD: bortezomib, lipsomal doxorubicin, dexamethasone

References

Bourgeault 2015

Bourgealt E, Dahl A, Thibeault MM, Dupéré A, Drolet AM, Mathieu J. 'POEMS Syndrome Complicated by Extensive Calciphylaxis: A Remarkable Recovery.' Journal of cutaneous medicine and surgery 2015 Mar 11. pii: 7750.2014.14086.

Braun 2011

Braun SA, Albrecht P, Methner A, Hanneken S. '[POEMS syndrome. An interdisciplinary clinical challenge].' Hautarzt. 2011 Oct;62(10):722-5. doi: 10.1007/s00105-011-2239-1. [Article in German]

Creamer 2014

Creamer A, Gaastra B, Odogwu S, Whitelaw B. 'POEMS syndrome: a challenging diagnosis of a rare disease.' Br J Hosp Med (Lond). 2014 Jul;75(7):408-9. doi: 10.12968/hmed.2014.75.7.408.

Haider 2013

Haider S, Latif T, Hochhausler A, Lucas F, Abdel Karim N. 'Waldenstrom's Macroglobulinemia and Peripheral Neuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes with a Bleeding Diathesis and Rash.' Case Rep Oncol Med 2013;2013:890864. doi: 10.1155/2013/890864.

He 2017

Haiyan He, Weijun Fu, Juan Du, Hua Jiang, Jian Hou. 'Successful treatment of newly diagnosed POEMS syndrome with reduced-dose bortezomib based regimen'. British journal of haematology first published: January 2017. DOI: 10.1111/bjh.14497

Hiyama 2016

Hiyama K, Terashima H, Kuroda A, Harada K, Shibagaki Y, Hosaka A, Hayashi T, Horiguchi H. 'The first case of POEMS syndrome with synchronous breast cancer: What are the associated diagnostic challenges?' Clinical case reports 2016 Mar 2;4(4):369-75. doi: 10.1002/ccr3.528.

Ishii 2013

Ishii Y, Yamazaki E, Ishiyama Y, Yamamoto E, Hattori Y, Hagihara M, Tomita N, Ishigatsubo Y. 'Successful treatment of POEMS syndrome with bortezomib and dexamethasone, combined with radiotherapy, and followed by autologous stem cell transplantation.' Int J Hematol 2013 Dec;98(6):723-8. doi: 10.1007/s12185-013-1456-z.

Kaygusuz 2010

Kaygusuz I, Tezcan H, Cetiner M, Kocakaya O, Uzay A, Bayik M. 'Bortezomib: a new therapeutic option for POEMS syndrome. Eur J Haematol 2010 Feb 1;84(2):175-7. doi: 10.1111/j.1600-0609.2009.01341.x.

Kim 2016

Kim EJ, Shin DH, Jeon HJ, Rhee SY, Nam ES, Park JY, Oh J. 'A Rare Case of Polyneuropathy and Monoclonalgammopathy with Recurrent Acute Kidney Injury'. Electrolyte Blood Press. 2016 Jun;14(1):5-10. doi: 10.5049/EBP.2016.14.1.5. Epub 2016 Jun 30.

Li 2011

Li LH, Zhang R, Tang XW. [Autologous hematopoietic stem cell transplantation following bortezomib-based chemotherapy for one case with POEMS syndrome]. Zhonghua Xue Ye Xue Za Zhi 2011 Nov;32(11):733. [Article in Chinese]

Li 2012

Li J, Zhang W, Kang WY, Cao XX, Duan MH, Zhou DB. 'Bortezomib and dexamethasone as first-line therapy for a patient with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes syndrome complicated by renal failure.' Leuk Lymphoma 2012 Dec;53(12):2527-9. doi: 10.3109/10428194.2012.690515.

Ohguchi 2011

Ohguchi H, Ohba R, Onishi Y, Fukuhara N, Okitsu Y, Yamamoto J, Ishizawa K, Ichinohasama R, Harigae H. 'Successful treatment with bortezomib and thalidomide for POEMS syndrome.' Ann Hematol 2011 Sep;90(9):1113-4. doi: 10.1007/s00277-010-1133-8.

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.

Sobas 2010

Sobas MA, Alonso Vence N, Diaz Arias J, Bendaña Lopez A, Fraga Rodriguez M, Bello Lopez JL. 'Efficacy of bortezomib in refractory form of multicentric Castleman disease associated to poems syndrome (MCD-POEMS variant).' Ann Hematol 2010 Feb;89(2):217-9. doi: 10.1007/s00277-009-0795-6.

Tang 2009

Tang X, Shi X, Sun A, Qiu H, Gu B, Zhou H, Xue S, Liu Y, Ruan C, Wu D. 'Successful bortezomib-based treatment in POEMS syndrome.' Eur J Haematol 2009 Dec 1;83(6):609-10. doi: 10.1111/j.1600-0609.2009.01330.x.

Wang 2011

Wang X, Ye S, Xiong C, Gao J, Xiao C, Xing X. 'Successful treatment with bortezomib and thalidomide for POEMS syndrome associated with multicentric mixed-type Castleman's disease.' Jpn J Clin Oncol 2011 Oct;41(10):1221-4. doi: 10.1093/jjco/hyr120.

Warsame 2012

Warsame R, Kohut IE, Dispenzieri A. 'Successful use of cyclophosphamide, bortezomib, and dexamethasone to treat a case of relapsed POEMS.' Eur J Haematol 2012 Jun;88(6):549-50. doi: 10.1111/j.1600-0609.2012.01780.x.

Yuan 2009

Yuan ZG, Dun XY, Li YH, Hou J. 'Treatment of multicentric Castleman's Disease accompanying multiple myeloma with bortezomib: a case report.' J Hematol Oncol 2009 Apr 28;2:19. doi: 10.1186/1756-8722-2-19.

Zeng 2013

Zeng K, Yang JR, Li J, Wei Q, Yang YM, Liu T, Niu T. 'Effective induction therapy with subcutaneous administration of bortezomib for newly diagnosed POEMS syndrome: a case report and a review of the literature.' Acta Haematol 2013;129(2):101-5. doi: 10.1159/000343681.

Zeng 2013a

Zeng K, Liu ZG, Yang JR, Hou L, Yang YM, Liu T, Niu T. '[Treatment for POEMS syndrome with subcutaneous administration of bortezomib followed by autologous peripheral blood stem cell transplantation: a case report and literatures review].' Zhonghua Xue Ye Xue Za Zhi 2013 Jun;34(6):550-2. doi: 10.3760/cma.j.issn.0253-2727.2013.06.023. [Article in Chinese]