Table 2.
Summary of Pivotal Trials Including Lenalidomide for Older Adults with Multiple Myeloma Who are Ineligible for High-Dose Therapy and Autologous Stem Cell Transplant
| Trial (Year) | Trial Phase | Older Adults Only |
Age, Median | High ECOG (0–1) or KPS (90–100) | Regimen | PFS | OS | Grade 3–4 Toxicities |
|---|---|---|---|---|---|---|---|---|
| Lenalidomide and Melphalan-Based Regimens | ||||||||
| GIMEMA MPR (2007) |
I/II | Yes | 71 | 43% | Induction: Melphalan, Prednisone, Lenalidomide Maintenance: Lenalidomide |
N/A | 100% | Cytopenias; febrile neutropenia; VTE |
| MM-015 (2012) |
III | Yes | 71 | Arms 1/2: 80 Arm 3: 90 *Median KPS |
Arm 1: MPR-R Arm 2: MPR Arm 3: MP |
Arm 1: 31 mo Arm 2: 14 mo Arm 3: 13 mo |
Arm 1: 70% Arm 2: 62% Arm 3: 66% |
Cytopenias; infections; VTE |
| E1A06 ECOG (2015) |
III | Yes | Arm 1: 75.8 Arm 2: 76.6 |
Arm 1: 81.2% Arm 2: 80.9% |
Arm 1: MPT-T Arm 2: mPR-R |
Arm 1: 21 mo Arm 2: 18.7 mo |
Arm 1: 52.6 mo Arm 2: 47.7 mo |
Cytopenias; VTE |
| MPT-T versus MPR-R (2016) | III | Yes | Arm 1: 72 Arm 2: 73 |
Arm 1: 81% Arm 2: 82% |
Arm 1: MPT-T Arm 2: MPR-R |
Arm 1: 20 mo Arm 2: 23 mo |
Arm 1: 73% Arm 2: 84% |
Peripheral neuropathy (MPT-T); neutropenia (MPR-R); infection; VTE |
| Lenalidomide and Dexamethasone-Based Regimens | ||||||||
| SWOG S0232 (2010) |
III | No | N/A | 85% | Induction: Arm 1: Lenalidomide; dexamethasone 40 mg Arm 2: Placebo; dexamethasone 40 mg Maintenance: Arm 1: Lenalidomide; dexamethasone 40 mg Arm 2: Placebo; dexamethasone 40 mg |
Arm 1: 78% Arm 2: 52% |
Arm 1: 94% Arm 2: 88% |
Neutropenia; VTE |
| E4A03 ECOG (2010) |
III | No | Arm 1: 66 Arm 2: 65 |
91% | Arm 1: Lenalidomide; dexamethasone 40 mg daily D1-4, 9–12, and 17–20 Arm 2: Lenalidomide; dexamethasone 40 mg |
N/A | Arm 1: 87% Arm 2: 96% |
Pneumonia; VTE |
| FIRST (2014) |
III | Yes | 73 | Arm 1: 77% Arm 2: 79% Arm 3: 79% |
Arm 1: Rd (continuous) Arm 2: Rd (18 cycles) Arm 3: MPT |
Arm 1: 25.5 mo Arm 2: 20.7 mo Arm 3: 21.2 mo |
Arm 1: 70% Arm 2: 66% Arm 3: 62% |
Neutropenia; infection |
| Triplet vs Doublet (2016) | III | Yes | Arm 1: 74 Arms 2/3: 73 |
Arm 1: 80 Arm 2: 90 Arm 3: 90 *Median KPS |
Arm 1: MPR Arm 2: CPR Arm 3: Rd *dosing differed for those >age 75 |
Arm 1: 24 mo Arm 2: 20 mo Arm 3: 21 mo |
Arm 1: 65% Arm 2: 68% Arm 3: 58% |
Neutropenia; infection |
| Rd-R vs Rd (2018) |
III | Yes | Arm 1: 75 Arm 2: 76 |
N/A | Arm 1: Induction: Lenalidomide 25 mg; dexamethasone 20 mg Maintenance: Lenalidomide 10 mg Arm 2: Lenalidomide 25 mg; dexamethasone 20 mg |
Arm 1: 18.3 mo Arm 2: 15.5 mo |
Arm 1: 85% at 18 mo Arm 2: 81% at 18 mo |
Neutropenia; infections; dermatologic reactions |
| Lenalidomide and Dexamethasone-Based Regimens in Relapsed/Refractory Disease | ||||||||
| RevLite (2017) | II | Yes | Arm 1: 69 | N/A | Arm 1: Lenalidomide 15 mg; dexamethasone 20 mg Arm 2: RD from matched cohort MM-009/MM-010 |
Arm 1: 8.9 mo Arm 2: 11 mo |
Arm 1: 30.5 mo Arm 2: 34.8 mo |
Infection; VTE (RD) |
| Real-world dosing (2017) | Retro. cohort |
Yes | 76.5 | 73% | Lenalidomide: 5–10 mg (66%), 15 mg (20%), 20–25 mg (14%); dexamethasone 20 or 40 mg | N/A | Dose 5–10 mg daily: 38.9 mo Dose >10 mg: not reached |
Cytopenias; fatigue; rash |
| Lenalidomide and Bortezomib-Based Regimens | ||||||||
| SWOG S0777 (2017) | III | No | 63 | Arm 1: 88% Arm 2: 84% |
Arm 1: VRd + Rd maintenance Arm 2: Rd |
Arm 1: 43 mo Arm 2: 30 mo |
Arm 1: 75 mo Arm 2: 64 mo |
Cytopenias; infection; VTE; peripheral neuropathy (VRd) |
| RVD-lite (2018) | II | Yes | 73 | 86% | Induction: Lenalidomide 15 mg; dexamethasone 20 mg; bortezomib Consolidation: lenalidomide; bortezomib |
35.1 mo | Not reached | Fatigue; hypo-phosphatemia; neutropenia |
| Lenalidomide and Daratumumab-Based Regimens | ||||||||
| MAIA (2019) | III | Yes | Arm 1: 73 Arm 2: 74 |
Arm 1: 82.9% Arm 2: 84% |
Arm 1: Lenalidomide 25 mg; dexamethasone 40 mg (or 20 mg if over age 75); Daratumumab Arm 2: Lenalidomide 25 mg; dexamethasone 40 mg (or 20 mg if over age 75) |
Arm 1: not reached Arm 2: 31.9 mo |
Arm 1: not reached Arm 2: not reached |
Cytopenias; infection |
Abbreviations: N/A, not available; mo, months; ECOG, Eastern Cooperative Oncology Group; KPS, Karnofsky Performance Status; PFS, progression-free survival; OS, overall survival; VTE, venous thromboembolism; M, melphalan, P, prednisone, R, lenalidomide; D, dexamethasone; T, thalidomide; V, bortezomib.