Table 3.
Single-agent use of rituximab. NHL non-Hodgkin's lymphoma, CLL chronic lymphocytic leukemia, SLL small lymphocytic lymphoma, MALT mucosa-associated lymphoid tissue, PTLD post-transplant lymphoproliferative disorders, MCL mantle-cell lymphoma, DLCL diffuse large cell lymphoma, CR complete response; PR partial response, ORR overall response rate
| Reference | Indication | Dose and schedule | No. of patientsa | Response rate | ||
|---|---|---|---|---|---|---|
| Indolent lymphoma: relapsed or refractory patients | ||||||
| [117 , 118] | Relapsed or refractory low-grade or follicular B-cell NHL | 375 mg/m2, 4× weekly | 166 | ORR=48% (6% CR, 42% PR) | ||
| Median DR=11.2 months | ||||||
| [61] | Relapsed or refractory follicular NHL | 375 mg/m2, 4× weekly | 70 | ORR=46% (3% CR, 43% PR) | ||
| Median DR=11 months | ||||||
| [181] | Recurrent indolent lymphoma | 375 mg/m2, 4× weekly | 34b | ORR=59% (24% CR, 35% PR) | ||
| Median DR=not available | ||||||
| Median TTP=16 months | ||||||
| [134] | Relapsed or refractory follicular, low-grade NHL | 375 mg/m2, 8× weekly | 37 | ORR=57% (14% CR, 43% PR) | ||
| Median DR and TTP not reached at 13.4+ and 19.4+ months, respectively | ||||||
| [10] | Relapsed or refractory follicular NHL | 375 mg/m2, 6× weekly | 17 | ORR=76% (47% CR, 29% PR) | ||
| Median DR=not available | ||||||
| [47, 48] | Rituximab-relapsed low-grade or follicular NHL | 375 mg/m2, 4× weekly | 60 | ORR=38% (10% CR, 28% PR) | ||
| Median DR=15.7+ months | ||||||
| Median TTP in responders=17.3+ months | ||||||
| [1]; pooled data from multiple studies | Relapsed or refractory, bulky disease, low-grade NHL | 375 mg/m2, 4× weekly | 39 | ORR=36% (3% CR, 33% PR) | ||
| Median DR=6.9 months | ||||||
| Indolent lymphoma: front-line patients | ||||||
| [38] | Front-line follicular NHL with low tumor burden | 375 mg/m2, 4× weekly | 49b | ORR=73% (26% CR, 47% PR) | ||
| Median DR=not available | ||||||
| [74] | Front-line low-grade or follicular NHL | 375 mg/m2, 4× weekly | 20 | ORR=50% | ||
| CR and PR not available | ||||||
| Median DR=not available | ||||||
| [75] | Front line in low-grade follicular NHL and CLL; followed by maintenance | 375 mg/m2, 4× weekly; at 6 months, if not PD, repeat courses every 6 months (not to exceed four repeats) | 60b | After first course: | ||
| ORR=47% (7% CR, 40% PR) | ||||||
| [77] | ≥First course (n=46): | |||||
| ORR=65% (27% CR, 38% PR) | ||||||
| Median DR=not available | ||||||
| Median progression-free survival >2 years | ||||||
| [66] | Front-line or relapsed/refractory patients with follicular NHL; followed by maintenance | Randomized, two cohorts: | 202 (58 front line) | In relapsed/refractory patients: ORR=46% | ||
| 375 mg/m2, 4× weekly | ||||||
| Followed by: | In front-line patients: ORR=66% | |||||
| Observation OR | Median event-free survival: | |||||
| Single infusion, months 3, 5, 7, and 9 | 22.4 months if maintenance | |||||
| 13.4 months if observation | ||||||
| Indolent lymphoma subsets | ||||||
| [56] | Front-line or relapsed/refractory Waldenstrom's macroglobulinemia | 375 mg/m2, 4× weekly; after 3 months if not PD, repeat course | 27 | ORR=44% (44% PR) | ||
| Median TTP in all patients: 16 months | ||||||
| [171] | Front-line or relapsed/refractory | 375 mg/m2, 4× weekly; after 3 months if not PD, repeat course | 22b | ORR=72.7% (50% PR, 22.7% minor response) | ||
| Waldenstrom's macroglobulinemia | ||||||
| Median time to treatment failure in responding patients: not reached | ||||||
| [169] | Front-line or relapsed/refractory | Retrospective analysis of several trials | 30b | ORR=60% (27% PR, 33% minor response) | ||
| Waldenstrom's macroglobulinemia | 375 mg/m2, 4× weekly; median of four infusions (range 1–11.3) | Median time to treatment failure in responders: 8 months | ||||
| [39] | Front-line or relapsed/refractory marginal zone (MALT type) | 375 mg/m2, 4× weekly | 35 | ORR=74% (49% CR, 25% PR) | ||
| Median DR=not available | ||||||
| Chronic lymphocytic leukemia | ||||||
| [87] | Relapsed or refractory CLL | 375 mg/m2, 4× weekly | 30 | ORR=23% (23% PR) | ||
| Median DR=20 weeks | ||||||
| [129] | Front-line or relapsed/refractory CLL or other mature B-cell lymphoid leukemias | Four weekly doses, dose 1 375 mg/m2 with dose escalation beginning at dose 2 (500 to 2, 250 mg/m2) | 45b (39b=CLL) | All patients: ORR=40% | ||
| Median TTP in responders: 8 months | ||||||
| In CLL patients: ORR=36% (all PR) | ||||||
| In CLL patients with highest dose, (2250 mg/m2): ORR=75% (all PR) | ||||||
| [20] | Front-line or relapsed SLL/CLL | First dose 100 mg then randomized to two cohorts: 250 (n=3) OR; 375 (n=30) mg/m2 thrice weekly for 4 weeks | 33 | In all patients: ORR=45% (3% CR, 42% PR) | ||
| Median DR: 10 months | ||||||
| [78] | Front-line and maintenance SLL/CLL | 375 mg/m2, 4× weekly | 56b | After first course: ORR=44% (9% CR, 35% PR) | ||
| At 6 months, if not PD, repeat courses every 6 months (not to exceed four repeats) | Median progression free-survival in first 24 patients: 35 months | |||||
| [167] | Front-line, early-stage CLL | 375 mg/m2, 8× weekly | 21b | ORR=86% (19% CR, 19% nodular PR, 48% PR) | ||
| Median DR=not available | ||||||
| Aggressive lymphoma | ||||||
| [36] | Relapsed or refractory aggressive lymphoma | Randomized, two cohorts: | 54 | ORR=31% (9% CR, 22% PR) | ||
| 1. 375 mg/m2, 8× weekly OR 2. 375 mg/m2 on day 1, followed by 500 mg/m2 7× weekly | 30 DLCL | DLCL patients: ORR=37% | ||||
| 13 MCL | MCL patients: ORR=33% | |||||
| 11 other | Median DR ≥246 days | |||||
| [62] | Front-line or relapsed mantle-cell, relapsed immunocytoma and small B-cell lymphocytic lymphoma | 375 mg/m2, 4× weekly | 120b | ORR=30% (8% CR, 22% PR) | ||
| Front-line MCL patients: ORR=38% | ||||||
| Relapsed MCL patients: ORR=37% | ||||||
| Median DR in MCL=1.2 years | ||||||
| [89] | Relapsed or refractory aggressive NHL | 375 mg/m2, 8× weekly | 57b | ORR=37% (12% CR, 25% PR) | ||
| Median DR=not available | ||||||
| Other lymphoproliferative diseases | ||||||
| [170] | Relapsed multiple myeloma | 375 mg/m2, 4× weekly | 19 | PR=5% | ||
| At 3 months, if not PD, second course | SD=27% | |||||
| [192] | Relapsed, classical Hodgkin's disease | 375 mg/m2, 6× weekly | 22b | ORR=23% | ||
| [57] | Lymphocyte-predominant Hodgkin's disease | 375 mg/m2, 4× weekly | 19b | ORR=100% (42% CR, 11% CRu, 47% PR) | ||
| [110] | Lymphocyte-predominant Hodgkin's disease | 375 mg/m2, 4× weekly | 9b | ORR=100% (67% CR, 33% PR) | ||
| [58] | PTLD | 375 mg/m2 weekly (1–9 infusions) | 12 | ORR=66% (66% CR) | ||
| [83] | PTLD | 375 mg/m2, 4× weekly | 13b | ORR=62% (23% CR) | ||
| [125] | PTLD | 375 mg/m2, 4× weekly, every 6 months | 8 | ORR=75% (37.5% CR) | ||
| Median duration of remission 5+ months | ||||||
aPatients in the intent-to-treat population are listed, unless otherwise noted
bEvaluable patients only