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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3872-3873
CORRESPONDENCE
To the editor:
Variable patterns of response to rituximab treatment in adults
with chronic idiopathic thrombocytopenic purpura
In a recent issue of Blood we reported that rituximab
anti-CD20 monoclonal antibody is an active drug in adults with chronic idiopathic thrombocytopenic purpura (ITP), that it is able to induce
long-lasting responses, and that in all responders a rise of the
platelet count occurs early during treatment, usually right after the
first antibody administration.1 We have now expanded our
series with 7 additional cases, in whom we observed somewhat different
patterns of response. Because patients with chronic ITP are being
recruited for phase 2 clinical trials with rituximab (browse the web
sites http://www.clinicaltrials.gov and
http://www.itppeople.com/clinical.htm for more information), we would
like to describe these cases. Patients' pretreatment characteristics are reported in Table
1. There were 6 women and 1 man, with a
median age of 40 years (range, 20-66 years). All cases had ITP that had
been resistant to between 2 and 6 different therapeutic regimens,
including 3 patients who had already failed splenectomy.
Rituximab schedule (375 mg/m2 intravenously once weekly for
4 consecutive weeks) and response criteria have been described
before.1
All patients concluded the 4 doses of treatment and could be evaluated
for response. As illustrated in Table 1, the platelet count rose to
greater than 50 × 109/L in 6 patients, with 4 achieving
a complete response (platelets > 100 × 109/L) and
2 a partial response (platelets > 50 × 109/L). In
5 of the responders (cases 1, 2, 4, 5, and 7) there was a marginal or
no increase of the platelet count during rituximab administration, with
responses appearing only 2 to 5 weeks after the last antibody infusion.
Peak platelet counts occurred 10 to 16 weeks after the start of
treatment, with a median peak count of 408 × 109/L
(range, 92 × 109/L to 751 × 109/L). Two
patients with complete remission (CR) have remained in remission with stable platelet counts during follow-up intervals of 7 to 12 or more months after the end of treatment. In the other 3 responders the follow-up is less than 6 months. In one patient (case 6), we observed an early but transient rise of the
platelet count after the first dose of rituximab, with a late response
beginning to appear at week 8 from the start of treatment and lasting 7 weeks. There were no significant changes of serum IgG, IgA, and IgM levels
throughout the study, whereas peripheral blood B-cell counts sharply
declined to near-zero values after the first dose of rituximab. Median
absolute T-cell counts as well as natural-killer cell counts remained
stable during the study period. No patient experienced adverse events
during therapy. Combining the results of our initial report with the present
data, we can identify 2 patterns of response, early and late. In early
responders there is an increase of the platelet count after the first
or second antibody infusion. The platelet count continues to rise
thereafter until a peak count, which is usually observed between week 6 and week 10. In late responders there is no rise of the platelet count
during rituximab administration, or there is just a marginal and
transient increase; in these cases platelets begin to rise at weeks 6 to 8 and very rapidly reach a peak count. How can one explain these 2 patterns of response? With the available data one can only speculate.
It is possible that in early responders opsonized B cells block the
macrophage system, a mechanism that reminds the mechanism of Fc
receptor (FcR) blockade by opsonized red cells following anti-D
immunoglobulin treatment.2 The decreased production of
antiplatelet antibodies accounts for the late and sustained response.
In late responders, the FcR blockade effect for some reason does not
work, and we only see the late response. In conclusion, our results confirm that rituximab is an active agent in
patients with chronic ITP and that the side effects of this treatment
are of mild entity. Contrary to our preliminary observations,1 responses can be expected not only early
during treatment but also up to 6 weeks after the last rituximab
infusion. Several issues about this agent, such as the optimum dose and treatment schedule, the exact mechanisms of action, and
long-term side effects, are the objectives of current investigations.
Roberto Stasi, Elisa Stipa, Vittorio Forte, Paola Meo, and Sergio Amadori
Correspondence: Roberto Stasi, Dept of Medical Sciences, Regina
Apostolorum Hospital, Via S Francesco, 50 00041 Albano Laziale, Italy;
e-mail: roberto.stasi{at}libero.it
References
1.
Stasi R, Pagano A, Stipa E, Amadori S.
Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura.
Blood.
2001;98:952-957[Abstract/Free Full Text].
2.
Bussel JB.
Fc receptor blockade and immune thrombocytopenic purpura.
Semin Hematol.
2000;37:261-266[CrossRef][Medline]
[Order article via Infotrieve].
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Related Article in Blood Online:
-
Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura
- Roberto Stasi, Adalberto Pagano, Elisa Stipa, and Sergio Amadori
Blood 2001 98: 952-957.
[Abstract]
[Full Text]
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