Hypereosinophilic syndrome

Section editor
	Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN

9 regimens on this page 9 variants on this page

All lines of therapy

Alemtuzumab monotherapy

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Regimen

Study	Evidence
Wagner et al. 2009	Case report

Chemotherapy

• Alemtuzumab (Campath) 30 mg IV bi-weekly

Duration not specified

References

1. Case report: Wagner LA, Speckart S, Cutter B, Gleich GJ. Treatment of FIP1L1/PDGFRA-negative hypereosinophilic syndrome with alemtuzumab, an anti-CD52 antibody. J Allergy Clin Immunol. 2009 Jun;123(6):1407-8. Epub 2009 Apr 1. link to original article contains protocol PubMed
2. Retrospective: Strati P, Cortes J, Faderl S, Kantarjian H, Verstovsek S. Long-term follow-up of patients with hypereosinophilic syndrome treated with Alemtuzumab, an anti-CD52 antibody. Clin Lymphoma Myeloma Leuk. 2013 Jun;13(3):287-91. Epub 2012 Nov 1. link to original article link to PMC article PubMed

Benralizumab monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Kuang et al. 2019 (NIAID 14-I-0081)	Randomized Phase II, <20 pts (E-esc)	Placebo	Seems to have superior primary endpoint

Chemotherapy

• Benralizumab (Fasenra) 30 mg SC once on day 1

28-day cycle for 6 or more cycles

References

1. NIAID 14-I-0081: Kuang FL, Legrand F, Makiya M, Ware J, Wetzler L, Brown T, Magee T, Piligian B, Yoon P, Ellis JH, Sun X, Panch SR, Powers A, Alao H, Kumar S, Quezado M, Yan L, Lee N, Kolbeck R, Newbold P, Goldman M, Fay MP, Khoury P, Maric I, Klion AD. Benralizumab for PDGFRA-negative hypereosinophilic syndrome. N Engl J Med. 2019 Apr 4;380(14):1336-1346. link to original article contains verified protocol link to PMC article PubMed

Cladribine & Cytarabine

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Regimen

Study	Evidence
Jabbour et al. 2005	Phase II, <20 pts

Note that the timing of drug administration is in hours in the manuscript, starting at t = 0 hours.

Chemotherapy

• Cladribine (Leustatin) 12 mg/m²/day IV continuous infusion over 120 hours, started on day 2 (total dose: 60 mg/m²)
• Cytarabine (Ara-C) 1000 mg/m² IV over 2 hours once per day on days 1, 3, 4, 5, 6

21-day cycle, repeated once if PR/CR; see text for definition of PR

References

1. Jabbour E, Verstovsek S, Giles F, Gandhi V, Cortes J, O'Brien S, Plunkett W, Garcia-Manero G, Jackson CE, Kantarjian H, Andreeff M. 2-Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic hypereosinophilic syndrome. Cancer. 2005 Aug 1;104(3):541-6. link to original article contains verified protocol PubMed

Hydroxyurea monotherapy

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Regimen

Study	Evidence
Parrillo et al. 1978	Non-randomized, <20 pts

To be completed; treatment details are not available in the abstract.

Chemotherapy

• Hydroxyurea (Hydrea)

References

1. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978 Aug;89(2):167-72. link to original article PubMed

Imatinib monotherapy

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Regimen

FDA-recommended dose

Study	Evidence
Gleich et al. 2002	Non-randomized, <20 pts
Apperley et al. 2002	Phase II, <20 pts
Pardanani et al. 2002	Phase II, <20 pts
Cortes et al. 2003	Phase II, <20 pts
Cools et al. 2003	Non-randomized, <20 pts
Klion et al. 2003	Non-randomized, <20 pts
Baccarani et al. 2007	Phase II
Helbig et al. 2008	Non-randomized, <20 pts
Metzgeroth et al. 2008	Phase II

Dosing is as described in the Metzgeroth et al. 2008 paper.

Chemotherapy

• Imatinib (Gleevec) as follows:
  • FIP1L1-PDGFRA positive patients: 100 mg PO once per day
  • PDGFRB fusion positive or without known molecular aberration: 400 mg PO once per day

28-day cycle for 13 or more cycles

Subsequent treatment

• Helbig et al. 2008: Patients proceeded to a maintenance phase after 3 to 6 months of therapy which consisted of weekly dosing; dose not specified in the manuscript

References

1. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet. 2002 May 4;359(9317):1577-8. link to original article PubMed
2. Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 2002 Aug 15;347(7):481-7. link to original article contains protocol PubMed
   1. Pooled Update: Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, Ross DM, Forrest D, Genet P, Rousselot P, Patton N, Smith G, Dunbar CE, Ito S, Aguiar RC, Odenike O, Gimelfarb A, Cross NC, Seymour JF. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014 Jun 5;123(23):3574-7. Epub 2014 Mar 31. link to original article link to PMC article PubMedPubMed PMID: 24687085
3. Pardanani A, Reeder T, Porrata LF, Li CY, Tazelaar HD, Baxter EJ, Witzig TE, Cross NC, Tefferi A. Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders. Blood. 2003 May 1;101(9):3391-7. Epub 2002 Dec 27. link to original article contains protocol PubMed
4. Cortes J, Ault P, Koller C, Thomas D, Ferrajoli A, Wierda W, Rios MB, Letvak L, Kaled ES, Kantarjian H. Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome. Blood. 2003 Jun 15;101(12):4714-6. Epub 2003 Feb 20. link to original article contains verified protocol PubMed
5. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003 Mar 27;348(13):1201-14. link to original article contains protocol PubMed
6. Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, Metcalfe DD, Dunbar C, Nutman TB. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2004 Jan 15;103(2):473-8. Epub 2003 Sep 22. link to original article contains protocol PubMed
7. Baccarani M, Cilloni D, Rondoni M, Ottaviani E, Messa F, Merante S, Tiribelli M, Buccisano F, Testoni N, Gottardi E, de Vivo A, Giugliano E, Iacobucci I, Paolini S, Soverini S, Rosti G, Rancati F, Astolfi C, Pane F, Saglio G, Martinelli G. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica. 2007 Sep;92(9):1173-9. Epub 2007 Aug 1. link to original article contains protocol PubMed
8. Helbig G, Stella-Hołowiecka B, Majewski M, Całbecka M, Gajkowska J, Klimkiewicz R, Moskwa A, Grzegorczyk J, Lewandowska M, Hołowiecki J. A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients. Br J Haematol. 2008 Apr;141(2):200-4. Epub 2008 Feb 26. link to original article contains protocol PubMed
9. Metzgeroth G, Walz C, Erben P, Popp H, Schmitt-Graeff A, Haferlach C, Fabarius A, Schnittger S, Grimwade D, Cross NC, Hehlmann R, Hochhaus A, Reiter A. Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study. Br J Haematol. 2008 Dec;143(5):707-15. Epub 2008 Oct 17. link to original article contains verified protocol PubMed

Mepolizumab monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Rothenberg et al. 2008 (GSK 100185)	Phase III (E-esc)	Placebo	Superior primary endpoint

Chemotherapy

• Mepolizumab (Nucala) 750 mg IV once on day 1

21-day cycle for 8 cycles

References

1. GSK 100185: Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. Epub 2008 Mar 16. Erratum in: N Engl J Med. 2008 Jun 5;358(23): 2530. link to original article contains verified protocol PubMed
   1. Update: Roufosse FE, Kahn JE, Gleich GJ, Schwartz LB, Singh AD, Rosenwasser LJ, Denburg JA, Ring J, Rothenberg ME, Sheikh J, Haig AE, Mallett SA, Templeton DN, Ortega HG, Klion AD. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013 Feb;131(2):461-7.e1-5. Epub 2012 Oct 4. link to original article PubMed

Nilotinib monotherapy

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Regimen

Study	Evidence
Kantarjian et al. 2006 (A2101)	Phase I/II, <20 pts of this subtype

Chemotherapy

• Nilotinib (Tasigna) 400 mg PO twice per day

References

1. A2101: Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. link to original article PubMed
   1. Subgroup analysis: Hochhaus A, le Coutre PD, Kantarjian HM, Baccarani M, Erben P, Reiter A, McCulloch T, Fan X, Novick S, Giles FJ. Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study. J Cancer Res Clin Oncol. 2013 Dec;139(12):1985-93. Epub 2013 Sep 22. link to original article PubMed

Peginterferon alfa-2a monotherapy

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Regimen

Study	Evidence
Butterfield et al. 2011	Case series

The authors describe using peginterferon alfa-2b initially but switched to peginterferon alfa-2a when the first was "no longer available. Dosing details are not available in the abstract."

Immunotherapy

• Peginterferon alfa-2a (Pegasys)

References

1. Case series: Butterfield JH, Weiler CR. Use of pegylated interferon in hypereosinophilic syndrome. Leuk Res. 2012 Feb;36(2):192-7. Epub 2011 Nov 26. link to original article PubMed

Ruxolitinib monotherapy

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Regimen

Study	Evidence
Rumi et al. 2013	Case report

Chemotherapy

• Ruxolitinib (Jakafi) 15 mg PO twice per day

Duration not specified

References

1. Case report: Rumi E, Milosevic JD, Casetti I, Dambruoso I, Pietra D, Boveri E, Boni M, Bernasconi P, Passamonti F, Kralovics R, Cazzola M. Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. J Clin Oncol. 2013 Jun 10;31(17):e269-71. Epub 2013 Apr 29. link to original article contains protocol PubMed