Table 2.
Trials using lenalidomide in combination in CLL patients.
| References | Regimen | No. | TLS % | TFR % | AE 3-4 (%) | Response |
|---|---|---|---|---|---|---|
| Chanan Khan [31] 2006-7 Phase II Relapsed or refractory |
Lenalidomide 10 mg per day escalated up to 5 mg each 1-2 week (max 25 mg) 21 days each 28 Rituximab 375 mg/m2 days 1, 8, and 15 (cycle 1) and days 1 and 15 (cycles 2–6) |
30 | 5 | 8 | Neutropenia 70% Thrombocytopenia 45% Anemia 18% |
ORR 57.7% RC 18% TFS 19.4 months ORR 38% (high risk cytogenetic) |
|
| ||||||
| James 2011 [30] Phase II frontline CLL Research Consortium CRC-014 |
Lenalidomide cycle 1: 2.5 mg; cycles 2–7: 5 mg escalated up to 10 mg (days 1–21 each 28) Rituximab: 50 mg/m2 day 29; 325 mg/m2 day 31; 375 mg/m2 day 33 (cycle 1), 375 mg/m2 weekly (cycle 2) and 375 mg/m2 day 1 (cycles 3–7) |
69 | 1.4 | Neutropenia 49% Thrombocytopenia 6% Anemia 11% |
ORR 95% (<65 y) ORR 78% (>65 y) RC 20% (<65 y) RC 8% (>65 y) TFS 19-20 m |
|
|
| ||||||
| Badoux [29, 43] Phase II relapsed or refractory |
Lenalidomide was started on day 9 at cycle 1 and on day 1 of the cycles 3–12: 10 mg continuously Rituximab 375 mg/m2 weekly during cycle 1 and on day 1 cycles 3 to 12 |
59 | 1.7 | 27 | Neutropenia 73% Thrombocytopenia 34% Anemia 15% Infection 15% |
ORR 66% RC 12% OS: 71% at 36 months TFS: 17.4 m |
|
| ||||||
| Veliz 2009 [32] Phase II Relapsed or progression after rituximab Heavily treated |
Lenalidomide cycle 1: 2.5 mg (days 1–7), 5 mg (days 8–15), 10 mg (15–21 days) followed by 7 days of rest and then 20 mg 21 each 28 days Rituximab 375 mg/m2 weakly each 4 weeks (day 15) |
10 | (RF) 12 | 12 | Neutropenia 41% | ORR 30% RC 0 |
|
| ||||||
| Chen 2012 [39] Phase II frontline |
Lenalidomide: 5 mg per day escalated 5 mg each 28 days (max 25 mg) Dexamethasone: 12 mg days 1–4; 14, 21, and 28 Maximum 18 cycles |
18 | 0 | 5 | Neutropenia 53% Neutropenia febrile 24% Thrombocytopenia 12% |
0R 59% RC 1% RP 53% |
|
| ||||||
| Badoux [33] Phase II Relapsed or refractory |
Lenalidomide 10 mg per day Ofatumumab weekly |
16 | NR | 13 | Neutropenia 50% Anemia 13% |
ORR 63% RC: 13% OS: NR TFS: NR |
|
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| Ferrajoli [44] 2012 Phase II Relapsed or refractory |
Lenalidomide 10 mg day 9 continued for 24 months Ofatumumab weekly for 3 weeks (300 mg week; 1000 mg week 2 and thereafter) monthly (months 2–6); every other month (months 7–24) |
36 | 0 | 0 | Neutropenia 47% Thrombocytopenia 9% Anemia 6% |
ORR 68% RC 24% |
|
| ||||||
| Blum [38] 2011 Phase I Relapsed or refractory very adverse |
Lenalidomide 2.5 mg escalating up to 25 mg days 1–21 Flavopiridol 30 mg/m2 in bolus followed of 30–50 mg/m2 days 1, 8, and 15 (cycle 1) and then days 3, 10 and 17 |
30 | 3 | 7 | Neutropenia 47% Thrombocytopenia 60% Anemia 33% |
ORR 57% RC: 0% OS 7 m TFS 23 m |
|
| ||||||
| GIMEMA [34] LLC 606 Phase I Relapsed or refractory |
Lenalidomide 2.5 mg escalating up to 15 mg Cyclophosphamide Fludarabine | 9 | 0 | 11 | Neutropenia transitory 3-4 in the majority of the patients | ORR 67% RC 33% NR NR |
|
| ||||||
| Egle [36] 2011 Phase I/II Frontline |
Lenalidomide 2.5 mg/day (days 7–21) escalating up to 25 mg (day 1–21) Fludarabine 40 mg/m2 1–3 Rituximab 375 m/m2 day 3 cycle 1; 500 mg/m2 day 1 cycles 2–6 Maintenance: R: 375 mg/m2 cycles 2, 4, and 6 Lenalidomide (maximum tolerated dose) |
45 | 0 | 0 | Neutropenia 88% | ORR 87% RC 49% NR NR |
|
| ||||||
| Flinn [45] 2012 Phase I-II Frontline |
Rituximab 375 mg/m2 (cycle 1); 500 mg/m2 (cycle 2–6) Fludarabine 25 mg/m2 (days 1–3) Lenalidomide 2.5–5 mg (days 8–28) 6 cycles |
51 | 6 | 0 | Neutropenia 47% Anemia 14% Thrombocytopenia 6 Rash 14% |
ORR: 78% RC 19% PFS 71% OS 88% (median FU 21 months) |
|
| ||||||
| Brown [35] Phase I Frontline |
Fludarabine: 25 mg/m2 (days 3–5) Rituximab: 50 mg/m2 day 1 and 325 mg/m2 day 3 Lenalidomide: 2.5 mg to alternate days (21 each 28 days) Followed by two cycles of consolidation with lenalidomide |
9 | 1/9 | 2/9 | Neutropenia 66% Thrombocytopenia 2/9 Allergy Syndrome hand-foot |
ORR 56% RC 1/9 |
TLS: tumor lysis syndrome; TFR: tumor flare reaction; AE: adverse effects; NR: not reported; ORR: overall response; CR: complete remission; OS: overall survival; TFS: treatment-free survival; y: year; m: month; RF: renal failure.