The effect of lenalidomide on rare blood disorders: Langerhans cell histiocytosis, multicentric Castleman disease, POEMS syndrome, Erdheim-Chester disease and angiomatosis


Authors: Z. Adam 1;  L. Pour 1;  M. Krejčí 1;  L. Zahradová 1;  P. Szturz 1;  R. Koukalová 2;  Z. Řehák 2;  T. Nebeský 3;  R. Hájek 1;  Z. Král 1;  J. Mayer 1
Authors‘ workplace: Interní hematologická a onkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc. 1;  Oddělení nukleární medicíny, centrum PET Masarykova onkologického ústavu Brno, přednosta prim. MUDr. Karol Bolčák 2;  Radiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Vlastimil A. Válek, CSc., MBA 3
Published in: Vnitř Lék 2012; 58(11): 856-866
Category: Case Reports

Overview

Lenalidomide has been licenced for the treatment of multiple myeloma and, in 2012, it is used as a standard treatment of relapses of the disease. Literature contains a number of publications on the effects of lenalidomide in myelodysplastic syndrome, in malignant lymphomas and chronic B lymphocytic leukaemia. The effects of the drug in rare diseases, however, have not been investigated so far. In this paper, we summarize our experience with lenalidomide in rare blood disorders. We observed an excellent effect of lenalidomide in multifocal aggressive, repeatedly relapsing Langerhans cell histiocytosis where it led to complete remission. This patient was treated with 2-chlorodeoxyadenosine and with CHOEP (cyclophosphamide, etoposide, doxorubicin, vincristine and prednisone) chemotherapy and high dose BEAM chemotherapy with autologous transplantation of haematopoietic tissue for an early disease relapse. Following another early relapse, the patient was treated with lenalidomide (25 mg). Treatment with lenalidomide induced complete remission on PET-CT. The patient was consolidated during the remission with a reduced intensity conditioning regimen and allogeneic transplantation of haematopoietic tissue. Following allogeneic transplantation, the patient has been in full remission for 10 months. We further showed an excellent effect of lenalidomide in multicentric Castleman disease with generalized involvement of lymphatic nodes, B symptoms and vasculitis. The patient was first treated R-CHOP chemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone). Due to a lack of efficacy, this was changed to the CVD combination (cyclophosphamide, thalidomide, dexamethazone). This treatment delivered complete remission but was complicated by thalidomide-associated neuropathy. Due to persistent neuropathy, thalidomide could not be used to manage further relapse and thus lenalidomide (25 mg, 11 cycles) was used. The patient has been in complete PET-CT remission for 7 months following this treatment. We observed partial efficacy in Erdheim-Chester disease. We used 2-chlorodeoxyadenosine as part of initial treatment that delivered partial regression of brain infiltrates only; fluorodeoxyglucose accumulation in the bones has not changed. Lenalidomide 25 mg was used as second line treatment. This led to complete regression of CNS infiltrates on MRI but fluorodeoxyglucose accumulation in bone lesions did not change. Regression of clinical signs and regression of fibrosis of retroperitoneum was achieved with an ongoing treatment with anakinra. A patient with multiple angiomatosis affecting the abdominal cavity, mediastinum and vertebrae and digestive tract had been stabilized with zoledronate (4 mg once every 2 months) and thalidomide (100 – 200 mg/den) for several years. However, several years of this treatment led to severe neuropathy. Consequently, we attempted to substitute thalidomide for lenalidomide. However, 10 mg of lenalidomide alone was not sufficiently effective and thus low dose of 50 mg of thalidomide was added. Combined treatment with zoledronate, lenalidomide 10 mg/day and thalidomide 50 mg/day stabilized the condition for 9 months. Due to relapsed gastrointestinal bleeding the treatment had to be changed after 9 months to thalidomide 100 mg/day and Sandostatin 0.1 mg twice daily s.c. A patient with osteosclerotic myeloma and POEMS syndrome was initially treated with CAD chemotherapy (cyclophosphamide, adriamycine and dexamethazone) that was followed by tandem high dose chemotherapy (melphalan 100 mg/m2) and autologous transplantation. Treatment with thalidomide was given due to insufficient efficacy but was not tolerated. Lenalidomide was administered as the fourth line treatment. Even though literature describes remission of POEMS syndrome following lenalidomide, four cycles did not lead to remission in our patient. Conclusion: We showed an effect of lenalidomide in Langerhans cell histiocytosis and in Castleman disease. The treatment led to regression of brain infiltrates in a patient with Erdheim-Chester disease. A dose of 10 mg of lenalidomide daily in combination with 50 mg of thalidomide stabilized a course of angiomatosis. Lenalidomide did not deliver the required treatment response in a patient with POEMS syndrome and multiple previous therapies.

Key words:
lenalidomide – thalidomide – cladribin – anakinra – Langerhans cell histiocytosis – Erdheim-Chester disease – Castleman disease – POEMS syndrome – angiomatosis


Sources

1. Sčudla V, Pika T, Budíková M et al. Příspěvek k hodnocení vztahů mezi angiogenními cytokiny, vybranými biologickými parametry a prognostickými faktory u mnohočetného myelomu. Čas Lék Česk 2006; 145: 929–935.

2. Sčudla V, Bačovský J, Indrák K et al. Výsledky léčby a změny v prognóze pacientů s mnohočetným myelomem v oblasti centrální a severní Moravy v posledních 40 letech. Vnitř Lék 2002; 48: 707–717.

3. Sčudla V. Anémie chronických chorob. Standardy pro diagnostiku a léčbu. Vnitř Lék 2002; 48: 422–426.

4. Minařík J, Pika T, Ba

ovský J et al. Prognostic value of hepatocyte growth factor, syndecan-1, and osteopontin in multiple myeloma and monoclonal gammopathy of undetermined significance. Scientific World Journal 2012; 2012: 356128. Epub 2012 Apr 26.

5. Minařík J, Sčudla V, Bačovský J et al. Comparison of imaging methods in POEMS syndrome. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012; 156: 52–57.

6. Sčudla V, Minařík J, Pika T. Light chain deposition disease. Vnitř Lék 2012; 58: 38–43.

7. Sčudla V, Petrová P, Minařík J et al. Analysis of the serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and different stages of multiple myeloma. Neoplasma 2011; 58: 499–506.

8. Minařík J, Sčudla V, Tichý T et al. Induction treatment of light chain deposition disease with bortezomib: rapid hematological response with persistence of renal involvement. Leuk Lymphoma 2012; 53: 330–331.

9. Sčudla V, Herman M, Minařík J et al. Přínos celotělové magnetické resonance pro diagnostiku monoklonální gammopatie nejistého významu a mnohočetného myelomu. VnitřLék 2011; 57: 52–60.

10. Myslivrček M, Bačovský J, Sčudla V et al. 18F-FDG PET/CT a 99mTc-MIBI scintigrafie při hodnocení pacientů s mnohočetným myelomem a monoklonální gamapatií nejistého významu. Srovnání metod. Klin Onkol 2010; 23: 325–331.

11. Bačovský J, Mysliveček M, Sčudla V et al. Tc-99m MIBI scintigraphy in multiple myeloma: prognostic value of different Tc-99m MIBI uptake patterns. Clin Nucl Med 2010; 35: 667–670.

12. Sčudla V, Pika T, Budíková M et al. The relationship between some soluble osteogenic markers, angiogenic cytokines/other biological parameters and the stages of multiple myeloma evaluated according to the Durie-Salmon and International Prognostic Index stratification systems. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2009; 153: 275–282.

13. Minařík J, Sčudla V, Ordeltová M et al. Prognostic significance of apoptotic index in multiple myeloma patients treated by conventional therapy and novel agents, thalidomide and bortezomib. Eur J Haematol 2009; 83: 528–534.

14. Krejci M, Scudla V, Tothova E, et al. Long--term outcomes of autologous transplantation in multiple myeloma: significant survival benefit of novel drugs in post-transplantation relapse. Clin Lymphoma Myeloma. 2009; 9 (6): 436-442.

15. Beličková M, Čermák J, Dostálová Merkerová M et al. Changes Associated With Lenalidomide Treatment in the Gene Expression Profiles of Patients With Del(5q). Clin Lymphoma Myeloma Leuk 2012; 12: 375-383.

16. Giagounidis AA, Kulasekararaj A, Germing U et al. Long-term transfusion independence in del(5q) MDS patients who discontinue lenalidomide. Leukemia 2012; 26: 855–858.

17. Segler A, Tsimberidou AM. Lenalidomide in solid tumors. Cancer Chemother Pharmacol 2012; 69: 1393–1406.

18. Gasent Blesa JM, Godoy MP, Esparcia MF et al. Response to Lenalidomide Therapy in a Pre-Treated Patient with Metastatic Prostate Cancer Refractory to Hormones and Chemotherapy: A Case Report. Case Rep Oncol 2012; 5: 181–186.

19. Holánek M, Hájek R. Použití lenalidomidu pro léčbu mnohočetného myelomu. Klin Onkol 2010; 23: 67–72.

20. Machálková K, Maisnar V. Léčba mnohočetného myelomu lenalidomidem. Klin Onkol 2009; 22: 117–120.

21. Novotová E, Neuwirtová R, Jonášová A et al. Lenalidomid (Revlimid) v léčbě mnohočetného myelomu – první zkušenosti v České republice. Čas Lék Česk 2008; 147: 623–626.

22. Kessler P. Profylaxe a léčbě trombembolismu v onkologii. Vnitř Lék 2009; 55: 219–222.

23. Radocha J, Maisnar V. Nízké dávky thalidomidu u refrakterního a relaxujícího myelomu. Vnitř Lék 2007; 53: 129–134.

24. Zbořil V. Idiopatické střevní záněty – současné léčebné možnosti. Vnitř Lék 2004; 50: (Suppl. 1): S94–S97.

25. Foldyna D, Kamelander J, Krejčí M et al. Žádoucí a nežádoucí účinky thalidomidu u pacientů s mnohočetným myelomem. Vnitř Lék 2003; 49: 859–868.

26. Habermann TM. New developments in the management of diffuse large B-cell lymphoma. Hematology 2012; 17: (Suppl. 1): S93–S97.

27. Chanan-Khan AA, Cheson BD. Lenalidomide for the treatment of B-cell malignancies. J Clin Oncol 2008; 26: 1544–1552.

28. Witzig TE, Wiernik PH, Moore T et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol 2009; 27: 5404–5409.

29. Dueck G, Chua N, Prasad A et al. Interim report of a phase 2 clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma. Cancer 2010; 116: 4541–4548.

30. Hernandez Ilizaliturri FJ, Deeb G, Zinzani PL et al. Higher response to lenalidomide in relapsed/refractory difusse large B-cell lymphoma in non germinal center B-cell lie then in germinal center B-cell like phenotype. Cancer 2011; 117: 5058–5066.

31. Zinzani PL, Pellegrini C, Gandolfi L et al. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk 2011; 11: 462–466.

32. Czuczman MS, Vose JM, Witzig TE et al. The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non-Hodgkin lymphoma of distinct histological origin. Br J Haematol 2011; 154: 477–481.

33. Witzig TE, Vose JM, Zinzani PL et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol 2011; 22: 1622–1627.

34. Tempescul A, Ianotto JC, Eveillard JR et al. Chemotherapy regimen associated to lenalidomide induces complete isotopic remission in Hodgkin’s lymphoma relapsing after autologous stem cell transplantation. Ann Hematol 2011; 90: 971–973.

35. Zaja F, De Luca S, Vitolo U et al. Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers. Haematologica 2012; 97: 416–422.

36. Habermann TM, Lossos IS, Justice G et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009; 145: 344–349.

37. Musuraca G, Fattori PP, Ceccolini M et al. Prolonged 18FDG-PET negative complete remission in a heavily pretreated, elderly patient with diffuse large B cell lymphoma treated with lenalidomide, low dose dexamethasone, and colony stimulating factor. Am J Hematol 2011; 86: 79–80.

38. Ivanov V, Tabouret E, Chuto G et al. Rituximab-lenalidomide-dexamethasone induces complete and durable remission in relapsed refractory diffuse large B-cell non-Hodgkin lymphoma. Leuk Lymphoma 2010; 51: 1758–1760.

39. Böll B, Borchmann P, Topp MS et al. Lenalidomide in patients with refractory or multiple relapsed Hodgkin lymphoma. Br J Haematol 2010; 148: 480–482.

40. Cox MC, Mannino G, Lionetto L et al. Lenalidomide for aggressive B-cell lymphoma involving the central nervous system. Am J Hematol 2011; 86: 957–958.

41. Chanan-Khan AA, Chitta K, Ersing N et al. Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response. Br J Haematol 2011; 155: 457–467.

42. Andritsos LA, Johnson AJ, Lozanski G et al. Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J Clin Oncol 2008; 26: 2519–2525.

43. Chanan-Khan A, Miller KC, Musial L et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 2006; 24: 5343–5349.

44. Ferrajoli A, Lee BN, Schlette EJ et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 2008; 111: 5291–5297.

45. Srinivasan S, Schiffer CA. Concurrent B-cell chronic lymphocytic leukemia and multiple myeloma treated successfully with lenalidomide. Leuk Res 2009; 33: 561–564.

46. Sher T, Miller KC, Lawrence D et al. Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics. Leuk Lymphoma 2010; 51: 85–58.

47. Badoux XC, Keating MJ, Wen S et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood 2011; 118: 3489–3498.

48. Chen CI, Bergsagel PL, Paul H et al. Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. J Clin Oncol 2011; 29: 1175–1181.

49. Wendtner CM. Lenalidomide in CLL: what is the optimal dose? Clin Adv Hematol Oncol 2011; 9: 220–224.

50. Giannopoulos K, Mertens D, Stilgenbauer S. Treating chronic lymphocytic leukemia with thalidomide and lenalidomide. Expert Opin Pharmacother 2011; 12: 2857–2864.

51. Pinto A, Corazzelli G, De Filippi R. Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response. Cancer 2012; 118: 1738–1739.

52. Arumainathan A, Kalakonda N, Pettitt AR. Lenalidomide can be highly effective in chronic lymphocytic leukaemia despite T-cell depletion and deletion of chromosome 17p. Eur J Haematol 2011; 87: 372–375.

53. Gentile M, Recchia AG, Vigna E et al. Lenalidomide in the treatment of chronic lymphocytic leukemia. Expert Opin Investig Drugs 2011; 20: 273–286.

54. Awan FT, Johnson AJ, Lapalombella R et al. Thalidomide and lenalidomide as new therapeutics for the treatment of chronic lymphocytic leukemia. Leuk Lymphoma 2010; 51: 27–38.

55. Sčudla V, Roček V, Dušek J et al. Multifokální eozinofilní granulom v dospělosti. Vnitř Lék 1987; 33: 1078–1086.

56. Adam Z, Řehák Z, Koukalová R et al. Lenalidomid indukoval léčebnou odpověď u pacienta s agresivní multisystémovou formou histiocytózy z Langerhansových buněk (LCH), rezistentní ke 2-chlorodeoxyadenosinu a časně relabující po vysokodávkované chemoterapii BEAM s autologní transplantací kmenových hemopoetických buněk. Vnitř Lék 2012; 58: 62–71.

57. Szturz P, Adam Z, Řehák Z et al. Lenalidomide proved effective in multisystem Langerhans cell histiocytosis. Acta Oncol 2012; 51: 412–415.

58. Adam Z, Šprláková A, Řehák Z et al. Parciální regrese ložisek Erdheimovy-Chesterovy nemoci v CNS po léčbě 2-chlorodeoxadenosinem a jejich kompletní vymizení při léčbě lenalidomidem. Popis případu a přehled literárních údajů. Klinická onkologie 2011; 24: 367–382.

59. Adam Z, Matýšková M, Tomíška M et al. Šestileté sledování pacienta s mnohočetnou angiomatózou postihující skelet, břišní i hrudní dutinu a stěnu trávicí trubice. Hodnocení vlivu zoledronatu, interferonu alfa, thalidomidu a lenalidomidu na aktivitu této nemoci. Klinická onkologie 2012; 25: 47–62.

60. Bowcock SJ, Patrick HE. Lenalidomide to control gastrointestinal bleeding in hereditary haemorrhagic telangiectasia: potential implications for angiodysplasias? Br J Haematol 2009; 146: 220–222.

61. Sumrall A, Fredericks R, Berthold A et al. Lenalidomide stops progression of multifocal epitheloid hemangioendothelioma including intracranial disease. J Neurooncol 2010; 97: 275–277.

62. Szturz P, Moulis M, Adam Z et al. Castleman disease. Klin Onkol 2011; 24: 424–434.

63. Ramasamy K, Gandhi S, Tenant-Flowers M et al. Rituximab and thalidomide combination therapy for Castleman disease. Br J Haematol 2012; 158: 421–423.

64. Wang X, Ye S, Xiong C et al. Successful treatment with bortezomib and thalidomide for POEMS syndrome associated with multicentric mixed-type Castleman’s disease. Jpn J Clin Oncol 2011; 41: 1221–1224.

65. Dispenzieri A. POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011; 86: 591–601.

66. Kim SY, Lee SA, Ryoo HM et al. Thalidomide for POEMS syndrome. Ann Hematol 2006; 85: 545–546.

67. Starkey CR, Joste NE, Lee FC. Near-total resolution of multicentric Castleman disease by prolonged treatment with thalidomide. Am J Hematol 2006; 81: 303–304.

68. Menegato MA, Canelles MF, Tonutti E et al. Remission of nephrotic syndrome after thalidomide therapy in a patient with Castleman’s disease. Clin Nephrol 2004; 61: 352–356.

69. Jung CP, Emmerich B, Goebel FD et al. Successful treatment of a patient with HIV-associated multicentric Castleman disease (MCD) with thalidomide. Am J Hematol 2004; 75: 176–177.

70. Lee FC, Merchant SH. Alleviation of systemic manifestations of multicentric Castleman’s disease by thalidomide. Am J Hematol 2003; 73: 48–53.

71. Stary G, Kohrgruber N, Herneth AM et al. Complete regression of HIV-associated multicentric Castleman disease treated with rituximab and thalidomide. AIDS 2008; 22: 1232–1234.

72. Zhao X, Shi R, Jin X et al. Diffuse hyperpigmented plaques as cutaneous manifestation of multicentric Castleman disease and treatment with thalidomide: report of three cases. J Am Acad Dermatol 2011; 65: 430–432.

73. Vannata B, Laurenti L, Chiusolo P et al. Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem-cell transplantation. Am J Hematol 2012; 87: 641–642.

74. Briani C, Manara R, Lessi F et al. Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy. Am J Hematol 2012; 87: 539–541.

75. Tomás JF, Giraldo P, Lecumberri R et al. POEMS syndrome with severe neurological damage clinically recovered with lenalidomide. Haematologica 2012; 97: 320–322.

76. Suyanı E, Yağcı M, Sucak GT. Complete remission with a combination of lenalidomide, cyclophosphamide and prednisolone in a patient with incomplete POEMS syndrome. Acta Haematol 2011; 126: 199–201.

77. Dispenzieri A, Armitage JO, Loe MJ,  et al. The clinical spectrum of

Castleman‘s disease. Am J Hematol. 2012; 87 (11): 997-1002.

78. Sethi S, Tageja N, Arabi H et al. Lenalidomide therapy in a rare case of POEMS syndrome with kappa restriction. South Med J 2009; 102: 1092–1093.

79. Dispenzieri A, Klein CJ, Mauermann ML. Lenalidomide therapy in a patient with POEMS syndrome. Blood 2007; 110: 1075–1076.

80. Szturz P, Adam Z, Chovancová J et al. Lenalidomide: a new treatment option for Castleman disease. Leuk Lymphoma 2011;53: 2089–2091.

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