Table 2.
Results from selected studies (n ≥ 30) in relapsed/refractory MM evaluating combinations of lenalidomide with conventional cytotoxic agents
| Study | Type of study | Regimen | Schedule | N | Prior treatment | Response | TTE | Key toxicities |
|---|---|---|---|---|---|---|---|---|
| Knop et al43 | Phase I/II | RAD | MTD not reached; highest dose-level: Len 25 mg on days 1–21 of 28-day cycle Doxo 9 mg/m2 on days 1–4 Dex 40 mg on days 1–4 and 17–20 |
69 | Median: 2 Thal: 20% Bort: 57% Len: 0% |
All evaluable patients ≥PR: 73% VGPR: 45% CR: 15% |
Median TTP: 45 weeks Median PFS: 40 weeks 1-year OS: 88% |
% of patients Grade ≥ 3 neutropenia: 48% Grade ≥ 3 thrombocytopenia: 38% Grade ≥ 3 anemia: 17% Grade ≥ 3 neurotoxicity: 0% Grade ≥ 3 venous thromboembolism: 2% |
| Baz et al44 | Phase I/II | Len-DVD | MTD: Len 10 mg on days 1–21 of 28-day cycle PLD 40 mg/m2 on day 1 VCR 2 mg on day 1 Dex 40 mg on days 1–4 |
62 | Median: 3 Thal: 66% Bort: 26% Len: 0% |
All evaluable patients ≥PR: 75% CR/nCR: 29% |
Median PFS: 12 months Median OS: not reached |
% of patients Grade ≥ 3 neutropenia: 32% Grade ≥ 3 thrombocytopenia: 13% Grade ≥ 3 anemia: 3% Grade ≥ 3 peripheral neuropathy: 5% Grade ≥ 3 venous thromboembolism: 9% |
| Reece et al50 | Phase I/II | CPR | MTD not reached; highest dose-level: Cyclo 300 mg/m2 po on days 1, 8, 15 of 28-day cycle Len 25 mg on days 1–21 Pred 100 mg every other day |
32 | Median: 2 Thal: 28% Bort: 50% Len: 0% |
All evaluable patients ≥MR: 94% |
1-year PFS: 78% 1-year OS: 93% |
% of patients Grade ≥ 3 neutropenia: 29% Grade ≥ 3 thrombocytopenia: 22% Grade ≥ 3 anemia: NA Grade ≥ 3 neurotoxicity: NA Grade ≥ 3 venous thromboembolism: 6% |
| Schey et al49 | Phase I/II | CRD | MTD: Cyclo 600 mg po on days 1, 8 of 28-day cycle Len 25 mg on days 1–21 Dex 20 mg on days 1–4, 8–11 Nine cycles, followed by Len maintenance |
31 | Median: 3 Thal: 90% Bort: 26% Len: 0% |
All evaluable patients ≥PR: 81% VGPR: 7% CR: 29% |
Median PFS: not reached 2-year PFS: 56% Median OS: not reached OS at 30 months: 80% |
% of patients Grade ≥ 3 neutropenia: 19% Grade ≥ 3 thrombocytopenia: NA Grade ≥ 3 anemia: NA Grade ≥ 3 neurotoxicity: 0% Grade ≥ 3 venous thromboembolism: 6% |
| Lentzsch et al45 | Phase I/II | BLD | MTD: Len 10 mg day 1–21 of a 28-day cycle Bendamustine 75 mg/m2 on days 1 and 2 Dex 40 mg on days 1, 8, 15, 22 |
36 | Median: 3 Thal: 48% Bort: NA Len: 79% |
All evaluable patients ≥PR: 52 VGPR: 24% CR: 0% |
Median PFS: 4.4 months Median OS: not reached |
% of patients Grade 4 neutropenia: 24.1% Grade 4 thrombocytopenia: 7% |
Abbreviations: MM, multiple myeloma; CR, complete response; nCR, near-complete response; VGPR; very good partial response; PR, partial response; NA, not available; TTE, time to events; TTP, time to progression; PFS, progression-free survival; OS, overall survival; Len, lenalidomide; Len-DVD, lenalidomide, pegylated liposomal doxorubicin, vincristine, and dexamethasone; MTD, maximum tolerated dose; po, oral administration; CRD, cyclophosphamide, lenalidomide, and dexamethasone; BLD, bendamustine, lenalidomide, and dexamethasone; Bort, bortezomib; Thal, thalidomide; Dex, dexamethasone; Pred, prednisone; Doxo, doxorubicin; Cyclo, cyclophosphamide; VCR, vincristine; PLD, pegylated liposomal doxorubicin.