Summary of studies (including ≥20 patients) evaluating rituximab therapy for TTP
| Reference . | Study design . | No. of patients . | Dose and schedule . | CR rate (%) . | Time to CR (days) . | Relapse rate . | Comments . |
|---|---|---|---|---|---|---|---|
| Upfront for the initial treatment of TTP | |||||||
| Scully et al7 | Prospective multicenter phase 2 (matched historical control group) | 40 (40 historical controls matched for age, sex, ethnicity, and number of relapses) | 375 mg/m2 per wk, 4 doses (up to 8 doses for persistent anti-ADAMTS13 antibodies) | 82.5 | 12 | 10% vs 57% in historical controls; median time to relapse, 27 (17-31) months for rituximab group and 18 (3-60) months for controls | Median duration of hospitalization was reduced by 7 d in patients who did not need intensive care admission; possible selection bias with controls who had a slightly higher relapse rate (57%) than shown in other cohorts; ADAMTS13 activity <10% was not confirmed in all patients |
| Westwood et al24 | Single-center retrospective case series | 100 (86 rituximab naive and 14 pretreated) | 375 mg/m2 per dose weekly or twice a week, 4 doses (up to 8 infusions for patients with persistent anti-ADAMTS13 antibodies) | 95, rituximab naive; 88, prior rituximab | 14 (4-52) | 13.4% Median time to relapse 24 (4-49) months | Earlier administration of rituximab (≤3 d or >3 d from admission) was associated with fewer TPEs for remission (16 vs 24, P = 0.03), and shorter median length of stay (16 vs 23 d, P = 0.01); similar response to weekly or twice-weekly dosing |
| Treatment of refractory or relapsed TTP | |||||||
| Scully et al20 | Case series | 25 (14 refractory and 11 relapsed) | 375 mg/m2 per wk, 4 doses | 100 | 11 (7-12) | No relapses at median follow up of 10 mo (range, 1-33 mo) | 21/25 patients had normal ADAMTS13 activity at 3 mo and 23/25 had no detectable inhibitor |
| Froissart et al14 | Prospective multicenter phase 2 | 21 (18 first episode, 3 relapsed) with matched historical controls | 375 mg/m2 per dose on days 1, 3, 7, and 14 after determination of refractory TTP | — | — | 40% (2 relapses at 6 mo and 51 mo) | ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after 3 mo in all patients |
| Clark et al6 | Prospective multicenter single arm phase 2 | 40 (20 refractory, 20 relapsed) | 375 mg/m2 per wk, 4 doses | Refractory: 63.6 at 8 wk, 88.9 at 1 y; relapsed: 90% at 8 wk, 100 at 1 y | — | — | — |
| Page et al22 | Single-center cohort | 16 (14 refractory) treated with rituximab and 21 not treated | 375 mg/m2 per wk, 4 doses | — | — | 12.5% in the rituximab treated group vs 42.8% in the non–rituximab-treated group | — |
| Treatment of persistent anti-ADAMTS13 antibodies in remission | |||||||
| Westwood et al24 | Single-center retrospective case series | 15 patients (21 episodes). | 375 mg/m2 per wk, 4 doses (n = 13) or 100 mg/m2 per wk, 4 doses (n = 2) | — | — | 1 relapse over median follow-up of 23 mo (range, 1-89 mo) | ADAMTS13 activity normalized at 3 mo in 16/17 episodes |
| Hie et al29 | Cross-sectional study | 30 treated with rituximab and 18 not treated with rituximab in remission | 375 mg/m2 per wk, 4 doses | — | — | 0 episodes/y and 0.5 episodes/y with and without preemptive rituximab, respectively | — |
| Westwood et al28 | Retrospective multicenter case series | 45 (76 episodes) | 375 mg/m2 per wk, 4 doses (n = 24);200 mg per wk, 4 doses (n = 19); and 500 mg per wk, 4 doses (n = 17) | — | — | 3.9% | All relapses occurred in the reduced-dose (200 mg/wk) group, which also had a high rate of retreatment |
| Reference . | Study design . | No. of patients . | Dose and schedule . | CR rate (%) . | Time to CR (days) . | Relapse rate . | Comments . |
|---|---|---|---|---|---|---|---|
| Upfront for the initial treatment of TTP | |||||||
| Scully et al7 | Prospective multicenter phase 2 (matched historical control group) | 40 (40 historical controls matched for age, sex, ethnicity, and number of relapses) | 375 mg/m2 per wk, 4 doses (up to 8 doses for persistent anti-ADAMTS13 antibodies) | 82.5 | 12 | 10% vs 57% in historical controls; median time to relapse, 27 (17-31) months for rituximab group and 18 (3-60) months for controls | Median duration of hospitalization was reduced by 7 d in patients who did not need intensive care admission; possible selection bias with controls who had a slightly higher relapse rate (57%) than shown in other cohorts; ADAMTS13 activity <10% was not confirmed in all patients |
| Westwood et al24 | Single-center retrospective case series | 100 (86 rituximab naive and 14 pretreated) | 375 mg/m2 per dose weekly or twice a week, 4 doses (up to 8 infusions for patients with persistent anti-ADAMTS13 antibodies) | 95, rituximab naive; 88, prior rituximab | 14 (4-52) | 13.4% Median time to relapse 24 (4-49) months | Earlier administration of rituximab (≤3 d or >3 d from admission) was associated with fewer TPEs for remission (16 vs 24, P = 0.03), and shorter median length of stay (16 vs 23 d, P = 0.01); similar response to weekly or twice-weekly dosing |
| Treatment of refractory or relapsed TTP | |||||||
| Scully et al20 | Case series | 25 (14 refractory and 11 relapsed) | 375 mg/m2 per wk, 4 doses | 100 | 11 (7-12) | No relapses at median follow up of 10 mo (range, 1-33 mo) | 21/25 patients had normal ADAMTS13 activity at 3 mo and 23/25 had no detectable inhibitor |
| Froissart et al14 | Prospective multicenter phase 2 | 21 (18 first episode, 3 relapsed) with matched historical controls | 375 mg/m2 per dose on days 1, 3, 7, and 14 after determination of refractory TTP | — | — | 40% (2 relapses at 6 mo and 51 mo) | ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after 3 mo in all patients |
| Clark et al6 | Prospective multicenter single arm phase 2 | 40 (20 refractory, 20 relapsed) | 375 mg/m2 per wk, 4 doses | Refractory: 63.6 at 8 wk, 88.9 at 1 y; relapsed: 90% at 8 wk, 100 at 1 y | — | — | — |
| Page et al22 | Single-center cohort | 16 (14 refractory) treated with rituximab and 21 not treated | 375 mg/m2 per wk, 4 doses | — | — | 12.5% in the rituximab treated group vs 42.8% in the non–rituximab-treated group | — |
| Treatment of persistent anti-ADAMTS13 antibodies in remission | |||||||
| Westwood et al24 | Single-center retrospective case series | 15 patients (21 episodes). | 375 mg/m2 per wk, 4 doses (n = 13) or 100 mg/m2 per wk, 4 doses (n = 2) | — | — | 1 relapse over median follow-up of 23 mo (range, 1-89 mo) | ADAMTS13 activity normalized at 3 mo in 16/17 episodes |
| Hie et al29 | Cross-sectional study | 30 treated with rituximab and 18 not treated with rituximab in remission | 375 mg/m2 per wk, 4 doses | — | — | 0 episodes/y and 0.5 episodes/y with and without preemptive rituximab, respectively | — |
| Westwood et al28 | Retrospective multicenter case series | 45 (76 episodes) | 375 mg/m2 per wk, 4 doses (n = 24);200 mg per wk, 4 doses (n = 19); and 500 mg per wk, 4 doses (n = 17) | — | — | 3.9% | All relapses occurred in the reduced-dose (200 mg/wk) group, which also had a high rate of retreatment |
CR, complete response.