Haematologica, Vol 94, Issue 3, 444-445 doi:10.3324/haematol.2008.001974
Copyright © 2009 by Ferrata Storti Foundation

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Letters to the Editor

Slow responses to standard dose rituximab in immune thrombocytopenic purpura. Author reply

Francesco Zaja, Renato Fanin

Clinica Ematologica, DIRM, Azienda Ospedaliera Universitaria, Udine, Italy

Corresponcence: Francesco Zaja, M.D., Clinica Ematologica, DIRM, Università degli Studi di Udine, Azienda Ospedaliera Universitaria, p.zza S. Maria della Misericordia, 33100 Udine, Italy. Phone: international +39.432.559604. Fax: international +39.432.559661. E-mail:zaja.francesco{at}aoud.sanita.fvg.it

Key words: immune thrombocytopenic purpura, Rituximab, kinetic of response.

We read the letter of Kelly et al.,¹ who report the results of their experience with standard dose rituximab (SD, i.e. 375 mg/m² weekly for four weeks) in patients with chronic immune thrombocytopenic purpura (ITP). Overall data are confirmatory to that previously reported by other authors: 6 out of 11 patients achieved a partial response (PR, platelet count > 50x10⁹/L) and 3 a complete response (CR, > 100x10⁹/L). The authors highlight that the time to CR was longer than expected (two months in 2 patients and six months in one), suggesting that a longer time of observation after rituximab therapy (at least six months) might be necessary before the decision regarding splenectomy.

Data from the literature indicate that in adult patients with ITP the response to SD rituximab develops more frequently early and often already within the fourth administration. Table 1 summarizes the results of some studies where data regarding the kinetic of response are available. In our previous study,² the median time to achieve PR and CR were 7 and 14 days respectively and only 3% and 10% of patients experienced PR and CR beyond the second and fourth month from the beginning of treatment.

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Table 1. Kinetic of response (complete and partial) after standard and low-dose rituximab.

In the reports of Stasi et al.³ and Giagounidis et al.⁴ all PRs and CRs were achieved within the first month of therapy. The paper of Cooper et al.,⁵ on the contrary, showed 3 different timings of CR, suggesting that a significant proportion of patients may achieve CR much later (33% between month +4 and +6). Finally, in his systematic review, Arnold et al.⁷ indicated a median time to response of 5.5 weeks from the first dose of rituximab in 123 valued patients with a range of 2–18 weeks. Different behavior can be seen with the use of low-dose rituximab (LD, i.e. 100 mg total dose weekly for four weeks), a very promising new therapeutic schedule for ITP. ^6,8

In our experience LD rituximab led to short and mid-term response rates similar to SD but with slower timing of response, with a median time to PR and CR of 31 and 44 days respectively⁶ (Table 1). Taken together these data indicate that in ITP the time to response to rituximab may be different according to clinical, biological and therapeutic variables.

We agree that, when possible, a period of at least six months of observation from rituximab therapy may be necessary before undergoing splenectomy since at present we still don’t have enough indicators predictive of brief and mid-term response.

References

1. Kelly K, Gleeson M, Murphy PT. Slow response to standard dose rituximab in immune thrombocytopenic purpura. Haematologica 2009;94:443-4.[Free Full Text]
2. Zaja F, Vianelli N, Battista M, Sperotto A, Patriarca F, Tomadini V, et al. Earlier administration of Rituximab allows higher rate of long lasting reponse in adult patients with autoimmune thrombocytopenia. Exp Hematol 2006;34:571-2.[CrossRef][Web of Science][Medline]
3. Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001;98:952-7.[Abstract/Free Full Text]
4. Giagounidis AA, Anhuf J, Schneider P, Germing U, Söhngen D, Quabeck K, et al. Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: a pilot study. Eur J Haematol 2002;69:95-100.[CrossRef][Web of Science][Medline]
5. 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;125:232-9.[CrossRef][Web of Science][Medline]
6. Zaja F, Battista ML, Pirrota MT, Palmieri S, Montagna M, Vianelli N, Luciana, et al. Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica 2008;93:930-3.[Abstract/Free Full Text]
7. 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;146:25-33.[Abstract/Free Full Text]
8. Provan D, Butler T, Evangelista ML, Amadori S, Newland AC, Stasi R. Activity and safety profile of low-dose rituximab for the treatment of autoimmune cytopenias in adults. Haematologica 2007;92:1695-8.[Abstract/Free Full Text]

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