Resumen
Introducción: la trombocitopenia inmune primaria (TIP) es una enfermedad autoinmune que puede causar hemorragias de diferente intensidad, las cuales llegan a poner en peligro la vida y alteran la calidad de vida de los pacientes. Puede ser tratada con rituximab como primera o segunda línea y la respuesta global es de 60%. Los mejores resultados se han observado en mujeres jóvenes con tiempo breve de evolución.
Objetivo: reportar la respuesta y la evolución clínica con el tratamiento de rituximab usado como un rescate en pacientes adultos con TIP en fase crónica o persistente de la enfermedad.
Material y métodos: se le administró rituximab de forma semanal por cuatro dosis a 31 pacientes adultos y se les hizo seguimiento durante un año.
Resultados: de los 31 pacientes adultos, se observó respuesta completa (RC, plaquetas ≥ 100 x 109/L) en 22 pacientes (71%) y respuesta parcial (RP, plaquetas ≥ 30 y ≤ 99x 109/L) en 5 pacientes (16%); la respuesta global fue de 87%. Tres pacientes recayeron durante el seguimiento y la respuesta sostenida (≥ 12 meses) se mantuvo en 24 pacientes, 21 (67%) con RC y 3 (10%) con RP. Los efectos secundarios fueron de leves a moderados en 13% de los pacientes.
Conclusiones: el rituximab demostró su utilidad en pacientes con TIP como tratamiento de rescate en las fases crónica y persistente. La respuesta sostenida ≥ 12 meses fue de 77%, con buena tolerancia y toxicidad aceptable.
Abstract
Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease that could cause different grades of bleeding, which could even threat the patients’ life or make them experience poor quality of life. ITP can be treated with rituximab either as a first or second-line therapy option, resulting in an overall response of 60%. The best results have been observed on young women with a short time of disease evolution.
Objective: To report the response and clinical evolution by providing therapy with rituximab, which was used as a rescue in adult patients with either persistent or chronical ITP.
Material and methods: 4 weekly doses of rituximab were administered to 31 adult patients and it was made a followup with them for a year.
Results: Out of the 31 patients, a complete response was observed (CR, platelets ≥ 100 x 109/L) in 22 patients (71%), and a partial response (PR, platelets ≥ 30 and ≤ 99 x 109/L) in 5 patients (16%); the global response was of 87%. 3 patients relapsed during follow-up and sustained response after rituximab (≥ 12 months) was held in 24 patients, 21 (67%) with CR and 3 (10%) with PR. Side effects were from low to moderate in 13% of patients.
Conclusions: Rituximab showed its effectiveness in patients with ITP as a rescue therapy in both chronical and persistent phases. Sustained response ≥ 12 months was of 77%, with good tolerance and acceptable toxicity.
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-93.
Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-86.
Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829-35.
Lucchini E, Zaja F, Bussel J. Rituximab in the Treatment of Immune Thrombocytopenia: What Is the Role of This Agent in 2019? Hematologica. 2019;104(6):1124-35.
Zaja F, Baccarani M, Mazza P, Bocchia M, Gugliotta L, Zaccaria A, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood. 2010; 115(14):2755-62.
Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013;121(11): 1976-81.
Newland A, Godeau B, Priego V, Viallard JF, López Fernández MF, Orejudos A, et al. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol. 2016;172(2): 262-73.
Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC, Gómez-De León A, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, et al. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014;123(25):3906-8.
Cuker A, Neunert C. How I treat refractory immune thrombocytopenia. Blood 2016;128(12):1547-54.
Medeot M, Zaja F, Vianelli N, Battista M, Baccarani M, Patriarca F, et al. Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. Eur J Haematol. 2008;81(3):165-9.
Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-207.
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829- 66. doi: 10.1182/bloodadvances.2019000966.
Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008;112 (4):999-1004.
Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhanet NB, et al. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9978):1653-61.
Marangon M, Vianelli N, Palandri F, Mazzucconi MG, Santoro C, Barcelliniet W, et al. Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response. Eur J Haematol. 2017;98(4):371-7.
Zaja F, Vianelli N, Battista M, Sperotto A, Patriarca F, Tomadini V, et al. Earlier administration of rituximab allows higher rate of long-lasting response in adult patients with autoimmune thrombocytopenia. Exp Hematol. 2006;34(5):571-2.
Khellaf M, Charles-Nelson A, Fain O, Terriou L, Viallard JF, Cheze S, et al. Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients. Blood. 2014;124(22):3228-36.
Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012; 119(25):5989-95.
Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25-33.
Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Update international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Advances 2019; 3 (22): 3780-817. DOI 10.1182/bloodadvances.2019000812.
Garcia-Chavez J, Majluf-Cruz A, Montiel-Cervantes L, Esparza MG, Vela-Ojeda J. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis. Ann Hematol. 2007;86(12):871-7.
Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98(4):952-7.
Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125(2):232-9.
Zaja F, Vianelli N, Volpetti S, Battista ML, Defina M, Palmieri S, et al. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010;85(4):329-34. doi: 10.1111/j.1600-0609.2010.01486.x.
Bussel JB, Lee CS, Seery C, Imahiyerobo AA, Thompson MV, Catellier D, et al. Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration. Haematologica. 2014;99(7):1264-71.
Chapin J, Lee CS, Zhang H, Zehnder JL, Bussel JB. Gender and duration of disease differentiate responses to rituximab– dexamethasone therapy in adults with immune thrombocytopenia. Am J Hematol. (2016);91(9):907-11.
Hasan A, Michel M, Patel V, Cunningham-Rundles S, Leonard JP, Bussel J. Repeated courses of rituximab in chronic ITP: three different regimens. Am J Hematol. 2009;84(10):661-5.
Khellaf M, Charles-Nelson A, Fain O, Terriou L, Viallard JF, Cheze S, et al. Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients. Blood. 2014;124(22):3228-36.
Chugh S, Darvish-Kazem S, Lim W, Crowther MA, Ghanima W, Wang G, et al. Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2015;2(2):e75-81.
Pavord S, Thachil J, Hunt BJ, Murphy M, Lowe G, Laffan M, et al. Practical guidance for the management of adults with immune thrombocytopenia during the COVID-19 pandemic. Br J Haematol 2020. doi: 10.1111/bjh.16775.
Houot R, Levy R, Cartron G, Armand P. Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine? Eur J Cancer. 2020;136:4 6. doi: 10.1016/j.ejca.2020.06.017.