Acquired thrombotic thrombocytopenic purpura

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

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Section editors
	Shruti Chaturvedi, MD, MSCI Baltimore, MD LinkedIn		Benjamin Tillman, MD Nashville, TN

5 regimens on this page 7 variants on this page

Initial therapy

Plasma exchange

Regimen

Study	Evidence	Comparator	Efficacy
Rock et al. 1991	Phase III	Plasma infusion	Seems to have superior OS

• Total plasma exchange as follows (minimum of 7 treatments in first 9 hospital days):
  • Treatments 1 to 3: Exchange of 1.5 times the predicted plasma volume
  • Treatments 4 onwards: Exchange of 1.0 times the predicted plasma volume

Supportive medications

• Dipyridamole (Persantine) 400 mg (route not specified) once per day for at least two weeks
• Aspirin 325 mg PO once per day for at least two weeks

References

1. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991 Aug 8;325(6):393-7. link to original article contains verified protocol PubMed

Relapsed or refractory

These treatments are usually used in addition to therapeutic plasma exchange, not in its place. There are also many treatments reported at the case report or case series level; the reader is guided to the 2015 Blood article, "How I treat refractory thrombotic thrombocytopenic purpura" for further details.

Methylprednisolone monotherapy

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Regimen #1, "High-dose"

Study	Evidence	Comparator	Efficacy
Balduini et al. 2009	Phase III	Standard-dose methylprednisolone	Might have superior CR rate

Immunosuppressive therapy

• Methylprednisolone (Solumedrol) as follows:
  • Days 1 to 3: 10 mg/kg/day IV
  • Days 4 to 23: 2.5 mg/kg/day IV

Regimen #2, "Standard-dose"

Study	Evidence	Comparator	Efficacy
Balduini et al. 2009	Phase III	High-dose methylprednisolone	Might have inferior CR rate

Immunosuppressive therapy

• Methylprednisolone (Solumedrol) as follows:
  • Days 1 to 3: 1 mg/kg/day IV
  • Days 4 to 23: 2.5 mg/kg/day IV

References

1. Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun;89(6):591-6. Epub 2009 Dec 23. link to original article contains protocol PubMed

Rituximab monotherapy

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Regimen #1

Study	Evidence
de la Rubia et al. 2010	Non-randomized
Clark et al. 2015	Phase II

Full text of de la Rubia et al. 2010 is not available for review.

Immunosuppressive therapy

• Rituximab (Rituxan) 375 mg/m² IV once per week

Supportive medications

• Prednisone (Sterapred) 50 mg PO once prior to Rituximab (Rituxan)
• Diphenhydramine (Benadryl) 50 mg PO once prior to Rituximab (Rituxan)
• Acetaminophen (Tylenol) 325 mg PO once prior to Rituximab (Rituxan)

4-week course

Regimen #2

Study	Evidence
Froissart et al. 2012	Non-randomized

Immunosuppressive therapy

• Rituximab (Rituxan) (dose not specified) IV

Four doses in 15 days

References

1. de la Rubia J, Moscardó F, Gómez MJ, Guardia R, Rodríguez P, Sebrango A, Zamora C, Debén G, Goterris R, López R, Peña F, Pujol M, Vidaller A, Del Río-Garma J, Sanz MA; Grupo Español de Aféresis. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci. 2010 Dec;43(3):299-303. Epub 2010 Oct 12. link to original article contains protocol PubMed
2. Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. PubMed
3. Review: Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015 Mar 5;125(10):1526-31. Epub 2015 Jan 8. Review. link to original article link to PMC article PubMed
4. Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR; members of the Canadian Apheresis Group. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015 Jul;170(2):208-17. Epub 2015 Apr 8. link to original article contains verified protocol PubMed

Vincristine monotherapy

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Regimen

Study	Evidence
Ferrara et al. 1999	Pilot, <20 patients

Chemotherapy

• Vincristine (Oncovin) 1.4 mg/m² IV once on day 1, then 1 mg IV once per day on days 4 & 7

References

1. Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G. Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol. 1999 Nov;78(11):521-3. contains protocol PubMed