Long‐term follow‐up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response

Abstract

Summary We report the long‐term follow‐up (median 39·5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty‐one responders had a platelet count >50 × 109/l at a median 20·2 months from treatment. Kaplan–Meier analysis showed a probability of relapse‐free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0·027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88·9% vs. 56·7%, P = 0·037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0·004) and sustained response (P = 0·002). Only mild and transient side‐effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow‐up.

The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia

“…In the 1-year follow-up of a prospective, multicenter trial of 4 weekly doses of rituximab (375 mg/m 2 ) 35 only 8 of 36 patients maintained their platelet counts above 50 ϫ 10 9 /L. 36 Higher response rates were found in some other trials [37][38][39][40] including one that allowed doubling of the dose if there was no response to the initial therapy. 39 Serum sickness has occurred in some patients 35,37,39 and the rate of more significant long-term adverse events such as progressive multifocal leukoencephalopathy remains uncertain.…”

Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia

“…The overall response rates, complete and partial, to initial treatment with rituximab (375 mg/m 2 ϫ 4) in adults and children with ITP were both 57% (Table 1). Two times as many responses in adults, as defined in the original reports, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][27][28][29] were complete responses (CR: platelet count Ͼ 150 ϫ 10 9 /L, 38%) as opposed to partial responses (PR: platelet count 50-150 ϫ 10 9 /L, 19%). In the 2 studies that assessed duration of effect according to type of initial response, patients achieving CRs had a greatly increased likelihood of maintaining their response at least 1 year from initial treatment compared with patients who achieved PRs.…”

“…In the 2 studies that assessed duration of effect according to type of initial response, patients achieving CRs had a greatly increased likelihood of maintaining their response at least 1 year from initial treatment compared with patients who achieved PRs. 6,27 Four studies 16,18,27,30 (Table 1) preliminarily assessed the durability of response in patients with ITP. The largest study, with 60 initially treated adults, reported a 43% 1-year response rate and a 40% 2-year response rate.…”

“…The autoimmune disorders treated with rituximab in addition to immune thrombocytopenic purpura (ITP) 4-18 include systemic lupus erythematosus (SLE), 19,20 vasculitis, 20 rheumatoid arthritis (RA), 21 autoimmune hemolytic anemia, 11,12,22 cryoglobulinemia, 23 acquired factor VIII Abs, 24 IgM polyneuropathies, 25 and thrombotic thrombocytopenic purpura. 26 As of 2011, at least 17 studies of rituximab treatment in children and adults with ITP accruing a minimum of 5 patients each had been reported, totaling 492 patients [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][27][28][29] (Table 1). The overall response rates, complete and partial, to initial treatment with rituximab (375 mg/m 2 ϫ 4) in adults and children with ITP were both 57% (Table 1).…”

Rituximab Used Successfully in the Treatment of Anti-NMDA Receptor Encephalitis

“…Thus, considering the B cell-selective pharmacological effects and the limited side effects of rituximab, this therapy might be particularly useful in young anti-NMDAR encephalitis patients without tumor lesions (2,5,7,13,14,20,(27)(28)(29)(30).…”