Immune thrombocytopenia

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 Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA
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20 regimens on this page
30 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASH

BSH

Initial therapy

Dexamethasone monotherapy

Regimen variant #1

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Cheng et al. 2003 1997-01 to 2000-12 Phase 2
Wei et al. 2015 (ITP-002) 2011-01 to 2014-05 Phase 3 (E-esc) Prednisone Superior CR rate (co-primary endpoint)

Immunosuppressive therapy

4-day course

Subsequent treatment

  • ITP-002, if platelets remained below 30 x 109/L or bleeding by day 10, course is repeated once
  • Cheng et al. 2003, patients who had an initial response, but whose platelets dropped below 30 x 109/L within 6 months received: Dexamethasone & Prednisone


Regimen variant #2, bi-weekly dexamethasone

Study Evidence
Mazzucconi et al. 2007 Phase 2

Immunosuppressive therapy

  • Dexamethasone (Decadron) by the following age-based criteria:
    • 15 years old or older: 40 mg IV or PO once per day on days 1 to 4
    • Younger than 15 years old: 20 mg/m2 (maximum dose of 40 mg) IV or PO once per day on days 1 to 4
  • Dexamethasone (Decadron) by the following response-based criteria:
    • Patients who had platelet counts of less than or equal to 30 x 109/L between cycles and/or who had bleeding related to thrombocytopenia: 0.035 mg/kg PO once per day "between courses"

14-day cycle for 4 cycles

References

  1. Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. Epub 2006 Oct 31. link to original article contains dosing details in manuscript PubMed
  3. ITP-002: Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. link to original article contains dosing details in manuscript PubMed NCT01356511

Dexamethasone & Eltrombopag

Regimen

Study Evidence
Gómez-Almaguer et al. 2014 Pilot, fewer than 20 pts reported

Immunosuppressive therapy

Growth factor therapy

5-week course

References

  1. Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC, Gómez-De León A, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, Tarín-Arzaga L, Hernández-Reyes J, Ruiz-Arguelles GJ. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014 Jun 19;123(25):3906-8. Epub 2014 May 6. link to original article contains dosing details in manuscript PubMed

Dexamethasone & Mycophenolate mofetil

Regimen

Study Evidence Comparator Efficacy
Bradbury et al. 2021 (FLIGHT) Phase 3 (E-esc) 1a. Dexamethasone
1b. Prednisolone 		Superior treatment failure (primary endpoint)

Immunosuppressive therapy

References

  1. FLIGHT: Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. link to original article PubMed NCT03156452

Dexamethasone & Prednisone

Regimen variant #1

Study Evidence Comparator Efficacy
Matschke et al. 2016 (EIS 2002) Phase 3 (E-esc) Prednisone Seems to have superior responding patients maintaining remission for at least 6 mo (secondary endpoint)

Immunosuppressive therapy

7-day course, then 21-day cycle for 6 cycles


Regimen variant #2

Study Dates of enrollment Evidence
Cheng et al. 2003 1997-01 to 2000-12 Phase 2

Preceding treatment

Immunosuppressive therapy

Indefinite course


Regimen variant #3, monthly dexamethasone

Study Evidence
Mazzucconi et al. 2007 Phase 2

Immunosuppressive therapy

  • Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
  • Prednisone (Sterapred) by the following response-based criteria:
    • Patients who had platelet counts of less than or equal to 20 x 109/L between cycles: 0.25 mg/kg PO once per day "between courses"

28-day cycle for 6 cycles


References

  1. Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. Epub 2006 Oct 31. link to original article contains dosing details in manuscript PubMed
  3. EIS 2002: Matschke J, Müller-Beissenhirtz H, Novotny J, Vester I, Hertenstein B, Eisele L, Lax H, Ose C, Dührsen U. A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment-Naïve Adult Patients with Immune Thrombocytopenia: EIS 2002 Study. Acta Haematol. 2016;136(2):101-7. Epub 2016 May 19. link to original article PubMed

Dexamethasone & Rituximab

Regimen ("R+3Dex")

Study Evidence
Imahiyerobo et al. 2013 Retrospective

Immunosuppressive therapy

14-day cycle for 3 cycles

References

  1. Abstract: Retrospective: Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. link to abstract

Intravenous immunoglobulin monotherapy

IVIG: IntraVenous ImmunoGlobulin

Regimen

Study Evidence Comparator Efficacy
Godeau et al. 1999 Phase 3 (E-esc) IVIG; 0.5 g/kg Superior response rate

Supportive therapy

One dose

References

  1. Imbach P, Wagner HP, Berchtold W, Gaedicke G, Hirt A, Joller P, Mueller-Eckhardt C, Müller B, Rossi E, Barandun S. Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet. 1985 Aug 31;2(8453):464-8. link to original article PubMed
  2. Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr. 1993 Dec;123(6):989-95. link to original article PubMed
  3. Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M, Esseltine D, Chan KW, de Veber B, Israels S, Kobrinsky N, Luke B. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. 1994 Sep 10;344(8924):703-7. link to original article PubMed
  4. Godeau B, Caulier MT, Decuypere L, Rose C, Schaeffer A, Bierling P. Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 05 and 1 g/kg bw. Br J Haematol. 1999 Dec;107(4):716-9. link to original article contains dosing details in abstract PubMed
  5. Godeau B, Chevret S, Varet B, Lefrère F, Zini JM, Bassompierre F, Chèze S, Legouffe E, Hulin C, Grange MJ, Fain O, Bierling P; French ATIP Study Group. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet. 2002 Jan 5;359(9300):23-9. link to original article PubMed
  6. TIKI: Heitink-Pollé KMJ, Uiterwaal CSPM, Porcelijn L, Tamminga RYJ, Smiers FJ, van Woerden NL, Wesseling J, Vidarsson G, Laarhoven AG, de Haas M, Bruin MCA; TIKI Investigators. Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood. 2018 Aug 30;132(9):883-891. Epub 2018 Jun 26. link to original article PubMed

Mycophenolate mofetil & Prednisolone

Regimen

Study Evidence Comparator Efficacy
Bradbury et al. 2021 (FLIGHT) Phase 3 (E-esc) 1a. Dexamethasone
1b. Prednisolone 		Superior treatment failure (primary endpoint)

Immunosuppressive therapy

References

  1. FLIGHT: Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. link to original article PubMed NCT03156452

Prednisone monotherapy

Regimen variant #1

Study Evidence Comparator Efficacy
Wei et al. 2015 (ITP-002) Phase 3 (C) Dexamethasone Inferior CR rate

Immunosuppressive therapy

  • Prednisone (Sterapred) as follows:
    • Days 1 to 28: 1 mg/kg/day PO
    • Day 29 onwards: tapered over 4 to 6 weeks with a goal of maintenance dosing less than 15 mg/day or "complete termination"
      • Taper schedule determined by treating physician

8- to 10-week course


Regimen variant #2

Study Evidence Comparator Efficacy
Matschke et al. 2016 (EIS 2002) Phase 3 (C) Dexamethasone Seems to have inferior responding patients maintaining remission for at least 6 mo

Immunosuppressive therapy

  • Prednisone (Sterapred) as follows:
    • Weeks 1 to 2: 1 mg/kg/day PO
    • Weeks 3 to 19: Tapered over 19 weeks with a goal of maintenance dosing less than 7.5 mg/day at the end of week 19

19-week course

References

  1. Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr. 1993 Dec;123(6):989-95. link to original article PubMed
  2. Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M, Esseltine D, Chan KW, de Veber B, Israels S, Kobrinsky N, Luke B. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. 1994 Sep 10;344(8924):703-7. link to original article PubMed
  3. ITP-002: Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. link to original article contains dosing details in manuscript PubMed
  4. EIS 2002: Matschke J, Müller-Beissenhirtz H, Novotny J, Vester I, Hertenstein B, Eisele L, Lax H, Ose C, Dührsen U. A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment-Naïve Adult Patients with Immune Thrombocytopenia: EIS 2002 Study. Acta Haematol. 2016;136(2):101-7. Epub 2016 May 19. link to original article PubMed

RhIG monotherapy

RhIG: Rho(D) Immune Globulin

Regimen variant #1, 25 mcg/kg

Study Evidence
Bussel et al. 1991 Phase 2

Eligibility criteria

  • RhD-positive

Supportive therapy

4-day course


Regimen variant #2, 50 mcg/kg

Study Evidence Comparator Efficacy
Newman et al. 2001 Randomized Phase 2, fewer than 20 pts (C) Rho(D); 75 mcg/kg Seems to have inferior platelet effect

Eligibility criteria

  • RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 109/L

Supportive therapy

Supportive therapy

One dose; can be repeated if required to increase platelet count


Regimen variant #3, 75 mcg/kg

Study Evidence Comparator Efficacy
Newman et al. 2001 Randomized Phase 2, fewer than 20 pts (E-esc) Rho(D); 50 mcg/kg Seems to have superior platelet effect

Eligibility criteria

  • RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 109/L

Supportive therapy

Supportive therapy

One dose; can be repeated if required to increase platelet count

References

  1. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991 May 1;77(9):1884-93. link to original article contains dosing details in manuscript PubMed
  2. Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/day of iv anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/day in adults with immune thrombocytopenic purpura. Br J Haematol. 2001 Mar;112(4):1076-8. link to original article contains dosing details in manuscript PubMed

TT4

TT4: Triple Therapy (4?)

Regimen

Study Evidence
Choi et al. 2015 Phase 2

Note: The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.

Immunosuppressive therapy

Dose and schedule modifications

  • Cyclosporine dose adjusted for target trough of 200 to 400 mcg/L

References

  1. Choi PY, Roncolato F, Badoux X, Ramanathan S, Ho SJ, Chong BH. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4). Blood. 2015 Jul 23;126(4):500-3. Epub 2015 May 13. link to original article contains dosing details in abstract link to PMC article PubMed

Relapsed or refractory

ATRA & Danazol

Regimen

Study Evidence Comparator Efficacy
Feng et al. 2017 (U1111-1132-6877) Randomized Phase 2 (E-esc) Danazol Superior 12-month sustained response (primary endpoint)

Targeted therapy

Endocrine therapy

16-week course

References

  1. U1111-1132-6877: Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. link to original article contains dosing details in abstract PubMed NCT01667263

Avatrombopag monotherapy

Regimen

Study Evidence Comparator Efficacy
Bussel et al. 2014 (AKR-501-CL-003) Phase 2
Bussel et al. 2014 (AKR-501-CL-004) Phase 2
Jurczak et al. 2018 (E5501-G000-302) Phase 3 (E-esc) Placebo Superior cumulative weeks of platelet response without rescue therapy for bleeding (primary endpoint)

Growth factor therapy

References

  1. AKR-501-CL-003: Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. Epub 2014 May 6. link to original article PubMed NCT00441090
  2. AKR-501-CL-004: Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. Epub 2014 May 6. link to original article PubMed NCT00625443
  3. E5501-G000-302: Jurczak W, Chojnowski K, Mayer J, Krawczyk K, Jamieson BD, Tian W, Allen LF. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018 Nov;183(3):479-490. Epub 2018 Sep 7. link to original article link to PMC article PubMed NCT01438840

Cyclosporine monotherapy

Regimen

Study Evidence
Emilia et al. 2002 Pilot, fewer than 20 pts

Note: The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.

Immunosuppressive therapy

  • Cyclosporine A as follows:
    • Days 1 to 6: 5 mg/kg/day PO split into twice per day dosing
    • Day 7 onwards: 2.5 to 3 mg/kg/day PO with dose adjusted for target trough of 200 to 400 mcg/L

References

  1. Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandini G, Ferrara L, D'Apollo N, Potenza L, Bertesi M, Torelli G. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15;99(4):1482-5. link to original article contains dosing details in manuscript PubMed

Danazol monotherapy

Regimen

Study Evidence Comparator Efficacy
Ahn et al. 1983 Pilot, >20 pts
Feng et al. 2017 (U1111-1132-6877) Randomized Phase 2 (C) ATRA & Danazol Inferior 12-month sustained response

Note: Ahn et al. 1983 gave a range of 200 mg PO from two to four times per day; the dose below is from U1111-1132-6877

Endocrine therapy

16-week course

References

  1. Ahn YS, Harrington WJ, Simon SR, Mylvaganam R, Pall LM, So AG. Danazol for the treatment of idiopathic thrombocytopenic purpura. N Engl J Med. 1983 Jun 9;308(23):1396-9. link to original article contains dosing details in manuscript PubMed
  2. U1111-1132-6877: Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. link to original article contains dosing details in abstract PubMed NCT01667263

Dexamethasone monotherapy

Regimen

Study Evidence
Andersen 1994 Pilot, fewer than 20 pts

Immunosuppressive therapy

28-day cycles for 6 cycles

References

  1. Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994 Jun 2;330(22):1560-4. link to original article contains dosing details in manuscript PubMed

Dexamethasone & Rituximab

Regimen ("R+3Dex")

Study Evidence
Imahiyerobo et al. 2013 Retrospective

Immunosuppressive therapy

14-day cycle for 3 cycles

References

  1. Abstract: Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. link to abstract

Eltrombopag monotherapy

Regimen variant #1

Study Evidence Comparator Efficacy
Grainger et al. 2015 (PETIT2) Phase 3 (E-esc) Placebo Superior durable platelet response (primary endpoint)

Note: This regimen was intended for pediatric patients.

Growth factor therapy

  • Eltrombopag (Promacta) with starting dose by the following age-, race-, and weight-based criteria:
    • 6 to 17 years old AND 27 kg or more AND NOT East Asian: 50 mg PO once per day
    • 6 to 17 years old AND 27 kg or more AND East Asian: 25 mg PO once per day
    • 6 to 17 years old AND less than 27 kg AND NOT East Asian: 37.5 mg PO once per day
    • 6 to 17 years old AND less than 27 kg AND East Asian: 25 mg PO once per day
    • 1 to 5 years old AND NOT East Asian: 1.2 mg/kg/day oral suspension
    • 1 to 5 years old AND East Asian: 0.8 mg/kg/day oral suspension

Dose adjusted to a maximum of 75 mg/day, with temporary discontinuation for platelet count greater than 400 x 109/L


Regimen variant #2

Study Evidence Comparator Efficacy
Bussel et al. 2009 (TRA100773) Phase 3 (E-esc) Placebo Superior plt count of greater than or equal to 50 x 109/L on day 43 (primary endpoint)

Growth factor therapy

The dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 x 109/L. Treatment was discontinued in patients who attained a platelet count greater than 200 x 109/L


Regimen variant #3

Study Evidence Comparator Efficacy
Cheng et al. 2010 (RAISE-ITP) Phase 3 (E-esc) Placebo Superior RR (primary endpoint)

Note: this trial should not be confused with the trial by the same name in colorectal cancer.

Growth factor therapy

6-month course

Dose and schedule modifications

  • Increase to 75 mg PO once per day allowed after day 22 for patients with platelet counts lower than 50 x 109/L
  • Decrease to 25 mg PO once per day required for platelets counts between 200 and 400 x 109/L
  • Drug was held for platelet count greater than 400 x 109/L, until platelet count dropped below 150 x 109/L


Regimen variant #4

Study Evidence Comparator Efficacy
Bussel et al. 2007 (TRA100773 phase 2) Randomized Phase 2 (E-esc) Placebo Superior RR (secondary endpoint)

Growth factor therapy

Up to 6-week course


Regimen variant #5

Study Evidence
Saleh et al. 2012 (EXTEND) Phase 2

Growth factor therapy

Dose and schedule were individualized with the goal of achieving and maintaining platelets between 50 and 200 x 109/L.

References

  1. TRA100773 phase 2: Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. link to original article PubMed NCT00102739
  2. TRA100773: Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. link to original article contains dosing details in manuscript PubMed NCT00102739
  3. RAISE: Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. link to original article contains dosing details in manuscript PubMed NCT00370331
  4. EXTEND: Saleh MN, Bussel JB, Cheng G, Meyer O, Bailey CK, Arning M, Brainsky A; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-45. Epub 2012 Nov 20. link to original article contains dosing details in manuscript PubMed
  5. PETIT2: Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. link to original article contains dosing details in manuscript PubMed NCT01520909
  6. Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. link to original article PubMed

Fostamatinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bussel et al. 2018 (FIT1) 2014-2016 Phase 3 (E-esc) Placebo Superior stable response (primary endpoint)
Bussel et al. 2018 (FIT2) 2015-01 to 2016-08 Phase 3 (E-esc) Placebo Superior stable response (primary endpoint)

Targeted therapy

24-week course

Dose and schedule modifications

  • Dose may be increased to 150 mg PO twice per day after 4 weeks if needed to achieve platelet count of at least 50 x 109/L

References

  1. FIT1: Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, Windyga J, Sivcheva L, Khalafallah AA, Zaja F, Cooper N, Markovtsov V, Zayed H, Duliege AM. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921-930. Epub 2018 May 15. link to original article link to PMC article PubMed NCT02076399
  2. FIT2: Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, Windyga J, Sivcheva L, Khalafallah AA, Zaja F, Cooper N, Markovtsov V, Zayed H, Duliege AM. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921-930. Epub 2018 May 15. link to original article link to PMC article PubMed NCT02076412
  3. Review: Newland A, Lee EJ, McDonald V, Bussel JB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018 Jan;10(1):9-25. link to original article PubMed

Mycophenolate mofetil monotherapy

Regimen

Study Evidence
Taylor et al. 2015 Retrospective

Immunosuppressive therapy

Continued indefinitely

References

  1. Retrospective: Taylor A, Neave L, Solanki S, Westwood JP, Terrinonive I, McGuckin S, Kothari J, Cooper N, Stasi R, Scully M. Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol. 2015 Nov;171(4):625-30. Epub 2015 Aug 6. link to original article PubMed

Placebo

Regimen

Study Evidence Comparator Efficacy
Kuter et al. 2008 (Amgen 20030105) Phase 3 (C) Romiplostim Inferior durable platelet response
Kuter et al. 2008 (Amgen 20030212) Phase 3 (C) Romiplostim Inferior durable platelet response
Bussel et al. 2009 (TRA100773) Phase 3 (C) Eltrombopag Inferior RR
Cheng et al. 2010 (RAISE-ITP) Phase 3 (C) Eltrombopag Inferior RR
Ghanima et al. 2015 (RITP) Phase 3 (C) Rituximab Did not meet primary endpoint of rate of treatment failure within 78 weeks
Grainger et al. 2015 (PETIT2) Phase 3 (C) Eltrombopag Inferior durable platelet response
Tarantino et al. 2016 (Amgen 20080279) Phase 3 (C) Romiplostim Inferior durable platelet response
Broome et al. 2023 (ADVANCE IV) Phase 3 (C) Efgartigimod Seems to have inferior sustained platelet count response (primary endpoint)

No active treatment; used as a comparator arm and here for reference purposes only. Note that RAISE should not be confused with the trial by the same name in colorectal cancer.

References

  1. Amgen 20030105: Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article PubMed NCT00102323
  2. Amgen 20030212: Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article PubMed NCT00102336
  3. TRA100773: Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. link to original article PubMed NCT00102739
  4. RAISE: Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. link to original article PubMed NCT00370331
  5. RITP: Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4. link to original article PubMed NCT00344149
  6. PETIT2: Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. link to original article PubMed NCT01520909
  7. Amgen 20080279: Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. link to original article PubMed NCT01444417
  8. Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. link to original article PubMed
  9. ADVANCE IV: Broome CM, McDonald V, Miyakawa Y, Carpenedo M, Kuter DJ, Al-Samkari H, Bussel JB, Godar M, Ayguasanosa J, De Beuf K, Rodeghiero F, Michel M, Newland A; ADVANCE Investigator Study Group. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Nov 4;402(10413):1648-1659. Epub 2023 Sep 28. link to original article PubMed NCT04188379

Rituximab monotherapy

Regimen

Study Evidence Comparator Efficacy
Godeau et al. 2008 Phase 2
Ghanima et al. 2015 (RITP) Phase 3 (E-esc) Placebo Did not meet primary endpoint of rate of treatment failure within 78 weeks

Patients in Godeau et al. 2008 had "ITP lasting 6 or more months before inclusion; at least 1 previous treatment for ITP; and platelet count less than 30 × 109/L at inclusion" and were candidates for splenectomy."

Immunosuppressive therapy

Supportive therapy

  • (per Godeau et al. 2008):
  • Patients received Streptococcus pneumoniae and Haemophilus influenzae vaccination at least 2 weeks before the first dose of rituximab
  • Acetaminophen (Tylenol) 1000 mg once on day 1, given prior to rituximab
  • Methylprednisolone (Solumedrol) 60 mg IV once on day 1, given prior to rituximab

7-day cycle for 4 cycles (4-week course)

References

  1. Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, Vekhoff A, Chauveheid MP, Stirnemann J, Galicier L, Bourgeois E, Haiat S, Varet B, Leporrier M, Papo T, Khellaf M, Michel M, Bierling P. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008 Aug 15;112(4):999-1004. Epub 2008 May 7. link to original article contains dosing details in manuscript PubMed
  2. Prospective cohort: Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, Kanter J, Neufeld E, Taube T, Ramenghi U, Shenoy S, Ward MJ, Mihatov N, Patel VL, Bierling P, Lesser M, Cooper N, Bussel JB. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012 Jun 21;119(25):5989-95. link to original article contains dosing details in manuscript link to PMC article PubMed
  3. RITP: Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4. link to original article contains dosing details in abstract PubMed NCT00344149

Romiplostim monotherapy

Regimen

Study Evidence Comparator Efficacy
Kuter et al. 2008 (Amgen 20030105) Phase 3 (E-esc) Placebo Superior durable platelet response (primary endpoint)
Kuter et al. 2008 (Amgen 20030212) Phase 3 (E-esc) Placebo Superior durable platelet response (primary endpoint)
Tarantino et al. 2016 (Amgen 20080279) Phase 3 (E-esc) Placebo Superior durable platelet response (primary endpoint)

Patients in Amgen 20030105 had undergone splenectomy. Patients in Amgen 20080279 were younger than 18 years old at time of study entry; see paper for details on dose titration.

Growth factor therapy

7-day cycles

References

  1. Amgen 20030105: Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article contains dosing details in manuscript PubMed NCT00102323
  2. Amgen 20030212: Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. link to original article contains dosing details in manuscript PubMed NCT00102336
  3. Amgen 20080279: Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. link to original article contains dosing details in manuscript PubMed NCT01444417

Vinblastine-loaded platelets

Regimen

Study Evidence Efficacy
Ahn et al. 1978 Phase 1 CR in 6 of 11 patients

References

  1. Phase 1: Ahn YS, Byrnes JJ, Harrington WJ, Cayer ML, Smith DS, Brunskill DE, Pall LM. The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets. N Engl J Med. 1978 May 18;298(20):1101-7. link to original article PubMed
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