Immune thrombocytopenia
Section editor | |
---|---|
Benjamin Tillman, MD Vanderbilt University Nashville, TN |
20 regimens on this page
31 variants on this page
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Guidelines
ASH
- 2019: Neunert et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia
Older
- 2011: Neunert et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia
BSH
"How I Treat"
- 2021: Ghanima et al. How I treat primary ITP in adult patients who are unresponsive to or dependent on corticosteroid treatment
Initial therapy
Dexamethasone monotherapy
Regimen variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wei et al. 2015 | Phase 3 (E-esc) | Prednisone | Superior CR rate |
Subsequent treatment
- If platelets remained below 30 x 109/L or bleeding by day 10, course is repeated once
Regimen variant #2
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 |
Immunosuppressive therapy, part 1
- Prednisone (Sterapred) 1 mg/kg/day PO for 7 days
Immunosuppressive therapy, part 2
- Dexamethasone (Decadron) 0.6 mg/kg/day (route not specified) for days 1 to 4
21-day cycle for 6 cycles
Regimen variant #3
Study | Evidence |
---|---|
Cheng et al. 2003 | Phase 2 |
Immunosuppressive therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
4-day course Patients who had an initial response, but whose platelets dropped below 30 x 109/L within 6 months received:
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Prednisone (Sterapred) 15 mg PO once per day, starting on day 5, "with gradual tapering"
Regimen variant #4, 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
- Patients who had platelet counts of less than or equal to 20 x 109/L between cycles received Prednisone (Sterapred) 0.25 mg/kg PO once per day "between courses"
28-day cycle for 6 cycles
Regimen variant #5, bi-weekly dexamethasone
Study | Evidence |
---|---|
Mazzucconi et al. 2007 | Phase 2 |
Immunosuppressive therapy
- Dexamethasone (Decadron) by the following criteria:
- Adults: 40 mg IV or PO once per day on days 1 to 4
- Patients less than 15 years old: 20 mg/m2 (maximum dose of 40 mg) IV or PO once per day on days 1 to 4
- 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 received 0.035 mg/kg PO once per day "between courses"
14-day cycle for 4 cycles
References
- 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
- 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
- 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
- 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 & Eltrombopag
Regimen
Study | Evidence |
---|---|
Gómez-Almaguer et al. 2014 | Pilot, <20 pts reported |
Immunosuppressive therapy
- Dexamethasone (Decadron) 40 mg/day PO on days 1 to 4
Growth factor therapy
- Eltrombopag (Promacta) 50 mg PO once per day on days 5 to 33
5-week course
References
- 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) | 1. Dexamethasone 2. Prednisolone |
Superior treatment failure |
Immunosuppressive therapy
References
- 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 & Rituximab
Regimen ("R+3Dex")
Study | Evidence |
---|---|
Imahiyerobo et al. 2013 | Retrospective |
Immunosuppressive therapy
- Dexamethasone (Decadron) 28 mg/m2/day (maximum dose of 40 mg) on days 1 to 4
- Rituximab (Rituxan) as follows:
- Cycles 1 & 2: 375 mg/m2 IV once per day on days 1 & 8
14-day cycle for 3 cycles
References
- 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 |
References
- 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
- 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
- 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
- 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
- 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
- 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) | 1. Dexamethasone 2. Prednisolone |
Superior treatment failure |
Immunosuppressive therapy
References
- 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 | 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
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
References
- 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
- 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
- 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
- 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
- Rho(D) immune globulin (RhoGAM) 25 mcg/kg IV once on day 1, repeated as needed on days 3 & 4
4-day course
Regimen variant #2, 50 mcg/kg
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Newman et al. 2001 | Randomized Phase 2, <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
- Rho(D) immune globulin (RhoGAM) 50 mcg/kg IV once on day 1
Supportive therapy
- Acetaminophen (Tylenol) 650 mg PO once on day 1, prior to therapy
- Prednisone (Sterapred) 20 mg PO once on day 1, prior to 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, <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
- Rho(D) immune globulin (RhoGAM) 75 mcg/kg IV once on day 1
Supportive therapy
- Acetaminophen (Tylenol) 650 mg PO once on day 1, prior to therapy
- Prednisone (Sterapred) 20 mg PO once on day 1, prior to therapy
One dose; can be repeated if required to increase platelet count
References
- 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
- 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
- Dexamethasone (Decadron) 40 mg/day PO on days 1 to 4
- Cyclosporine A 2.5 to 3 mg/kg/day PO on days 1 to 28
- Dose adjusted for target trough of 200 to 400 mcg/L
- Rituximab (Rituxan) 100 mg IV once per day on days 7, 14, 21, 28
References
- 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 |
Targeted therapy
- All-trans retinoic acid (ATRA) 10 mg PO twice per day
Endocrine therapy
- Danazol (Danocrine) 200 mg PO twice per day
16-week course
References
- 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 |
Growth factor therapy
References
- 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
- 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
- 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, <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
- 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
References
- 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
- 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, <20 pts |
Immunosuppressive therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycles for 6 cycles
References
- 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
- Dexamethasone (Decadron) 28 mg/m2/day (maximum dose of 40 mg) on days 1 to 4
- Rituximab (Rituxan) as follows:
- Cycles 1 & 2: 375 mg/m2 IV once per day on days 1 & 8
14-day cycle for 3 cycles
References
- 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 |
Note: This regimen was intended for pediatric patients.
Growth factor therapy
- Eltrombopag (Promacta) with starting dose by the following criteria:
- Age 6 to 17, weighing at least 27kg, non-east Asian: 50 mg PO once per day
- Age 6 to 17, weighing at least 27kg, east Asian: 25 mg PO once per day
- Age 6 to 17, weighing less than 27kg, non-east Asian: 37.5 mg PO once per day
- Age 6 to 17, weighing less than 27kg, east Asian: 25 mg PO once per day
- Age 1 to 5, non-east Asian: 1.2 mg/kg/day oral suspension
- Age 1 to 5, 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 |
Growth factor therapy
- Eltrombopag (Promacta) 50 mg (starting dose) PO once per day
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 |
Note: this trial should not be confused with the trial by the same name in colorectal cancer.
Dose 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 3 (E-esc) | Placebo | Superior RR |
Regimen variant #5
Study | Evidence |
---|---|
Saleh et al. 2012 (EXTEND) | Phase 2 |
Growth factor therapy
- Eltrombopag (Promacta) 50 mg PO once per day, with adjustments:
Dose and schedule were individualized with the goal of achieving and maintaining platelets between 50 and 200 x 109/L.
References
- TRA100773: 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
- 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
- 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
- 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
- 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
- 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 |
Bussel et al. 2018 (FIT2) | 2015-2016 | Phase 3 (E-esc) | Placebo | Superior stable response |
Targeted therapy
- Fostamatinib (Tavalisse) 100 mg PO twice per day
- Dose may be increased to 150 mg PO twice per day after 4 weeks if needed to achieve platelet count of at least 50
24-week course
References
- 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
- 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
- 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 |
References
- 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 |
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
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 (Rituxan)
- Acetaminophen (Tylenol) 1000 mg once per day on days 1, 8, 15, 22, prior to Rituximab (Rituxan)
- Methylprednisolone (Solumedrol) 60 mg IV once per day on days 1, 8, 15, 22, prior to Rituximab (Rituxan)
4-week course
References
- 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. link to original article contains dosing details in manuscript PubMed
- 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
- 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 |
Kuter et al. 2008 (Amgen 20030212) | Phase 3 (E-esc) | Placebo | Superior durable platelet response |
Tarantino et al. 2016 (Amgen 20080279) | Phase 3 (E-esc) | Placebo | Superior durable platelet response |
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
- Romiplostim (Nplate) 1 mcg/kg SC once per day on days 1, 8, 15, 22
28-day cycles
References
- 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
- 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
- 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 |
Reference
- Phase 1: Ahn YS, Byrnes JJ, Harrington WJ, Cayer ML, Smith DS, Brunskill DE, Pall LM. New England Journal of Medicine. 1978; 298:1101-1107. link to original article PubMed