Table 2.
Selected induction regimens for elderly patients with reported outcomes and adverse events.
| Reference | Patients | Median age (range) | Regimen | Response rate | Median PFS (months) | Median OS (months) | Grade 3–4 AEs | Notes/Dose adjustments |
|---|---|---|---|---|---|---|---|---|
| Palumbo et al., Blood, 2015 [5] | 869 A: Fit 340 B: Int 269 C: Frail 260 |
74 (70–78) | Len-based 76%; Prot. inhib-based 24% |
N/R | 3-yr OS A: 48% B: 41% C: 33% |
3-yr OS A: 84% B: 76% C: 57% |
Hem/Non-hem A: 38%/18% B: 35%/22% C: 30%/30% |
Reduced/Discontinued A: 21%/17% B: 22%/22% C: 16%/25% |
| Facon et al., Lancet, 2007 (IFM 99–06 trial) [12] | 195 | 65–75 | MPT | ORR 76% CR 13% VGPR 34% PR 29% |
27.5 | 51.6 | Hem: A 14%/N 48%/T 14% VTE 12% Peripheral neuropathy 6% Somnolence 8% Infections 13% Cardiac arrhythmia 2% Constipation 10% |
TRM: 0%. Starting Thalidomide: 52% ≤200mg/d 48% >200mg/d Dose increased: 9%; Dose reduced: 40%; Discontinued: 45% due to AE. |
| San Miguel et al., NEJM, 2008; Mateos et al., Lancet Oncol, 2010; San Miguel et al., JCO, 2013 (VISTA trial) [22–24] | 340 | 71 (57–90) | VMP | ORR 74% CR 34% VGPR 8% PR 33% SD 23% POD 1% |
21.7 | 56.4; 3-yr OS 68.5% |
Hem: A 19%/N 40%/T 37% GI: N/V 4% Diarrhea 8% Infections: PNA 7% Zoster 3% Pyrexia 3% CNS: Neuralgia 9% Peripheral neuropathy 13% Others: Fatigue 8% Anorexia 3% Asthenia 6% Dyspnea 4% Hypokalemia 7% |
TRM 1%. Discontinuation due to AE: 15%; Bortezomib alone discontinued in 19%. |
| Mateos et al., Lancet Oncol, 2010 [23] |
130 | 73 (69–76) | VTP | ORR 81% CR 28% VGPR 8% PR 45% SD 17% POD 2% |
25 | 3-yr OS 65% | Hem: A 8%/N 22%/T 12% Cardiac 8% Neuropathy 9% Infections 1% GI 2% VTE 2% |
TRM 5%. Discontinuation due to AE: 17%. |
| Benboubker et al., NEJM, 2014 [25] |
535 | 73 (44–91) | Rd (continuous) | ORR 75% CR 15% VGPR 28% PR 32% SD 19% POD 1% |
25.5 | 3-yr OS 70% | Hem: A 18%/N 28%/T 8% Infection 29% Cardiac 12% VTE 8% Asthenia 8% Fatigue 7% Back pain 7% Hypokalemia 7% Hyperglycemia 5% Rash 6% Cataracts 6% Dyspnea 6% Constipation 2% 2nd cancer 3% |
Multiple dose modifications per pre-determined protocol |
| Durie et al., Lancet, 2017 [32] | 242 | 63 (IQR 56–70) | VRd | ORR 81% CR 16% VGPR 28% PR 38% SD 16% POD 3% |
43 | 75 | Hem: 47% Neuropathy 33% Infection 15% Constitutional 20% GI 22% Cardiac 7% Vascular 9% 2nd cancers 1% |
23% discontinuation due to AE (others at time of achieving disease control); no discontinuation due to AE |
| Moreau et al., Blood, 2015 [34] | 68 | 72 (66–86) | CMP | ORR 90% CR 12% VGPR 46% PR 32% SD 10% POD 0% |
21 | 3-yr OS 80% | Hem: A 35%/N 38%/T 28% Infections 7% GI: Nausea 6% Elevated LFTs 4% Cardiovascular: CHF 4% Afib 1.5%, HTN 3% DVT 1.5% Peripheral neuropathy 1.5% AKI 3% Fatigue 3% |
No treatment discontinuation in any patient; dose reduction not reported |
| Mateos et al., Blood, 2016 [38] | 233 | 75 (65–89) | VMP-Rd Sequential or Alternating |
ORR 78% CR 24% VGPR 22% PR 15% SD 3% POD 14% |
33 | 3-yr OS 73% | Hem: A 3%/N 21%/T 21% Infections 6% GI 6% VTE 3% Rash 5% Peripheral neuropathy 3% |
TRM 6%. Discontinuation 14% in sequential (6.4% SAE) vs. 18% in alternating (9.3% SAE) scheme. |
| Zepeda et al., Blood, 2014 (Abstract) [39] | 20 | 76 (66–90) | CyBorD (VCD) | ORR 95% CR 15% VGPR 55% PR 25% SD 5% POD 25% |
N/R | N/R | Hem: 10% Non-hem (20%): PNA Muscle weakness Sepsis |
10% dose-reduction; 5% discontinuation cyclophosphamide due to cytopenia |
| Palumbo et al., JCO, 2014 [40] | 250 | 71 (IQR 68–75) | VMPT-VT | ORR 89% CR 38% VGPR 21% PR 30% SD 6% POD 1% |
35.3; 3-yr PFS 56% |
3-yr OS 89%; 5-yr OS 61% |
Hem: A 10%/N 38%/T 22% Fatigue 6% Cardiac (11%): CHF 3% Arrhythmia 4% MI/angina 2% CNS (21%): Neuralgia 4% Neuropathy 11% Both 4% Infections (13%): PNA 6% Neutrop fever 2% Sepsis 2% Other 2% GI 6% VTE 5% Others 11% |
TRM 4%. Discontinuation due to AE: 28%; ≤75years: 25% had dose interruption due to AEs with 81% of planned bortezomib dose intensity given over median 24 months; >75years: 35% had dose interruption due to AEs with 58% of planned bortezomib dose intensity given over median 11 months. |
| Zweegman et al., Blood, 2016 [49] | 319 318 |
73 (60–87) 72 (60–91) |
MPR MPT |
ORR 84% CR 11% VGPR 45% PR 39% ORR 81% CR 10% VGPR 37% PR 34% |
23 20 |
3-yr OS 69%; 4-yr OS 56% 3-yr OS 64%; 4-yr OS 52% |
Hem: A 14%/N 64%/T 30% Neuropathy 1% VTE 8% Hem: A 5%/N 27%/T 8% Neuropathy 7% VTE 8% |
Discontinuations mostly due to AEs: 41% in MPR, 49% in MPT; mainly occurred in pts >75 (51 vs. 32%). |
N/R: not reported; IQR: interquartile range; Hem: Hematologic; A/N/T: Anemia/Neutropenia/Thrombocytopenia; ORR: overall response rate; VGPR: very good partial response; PR: partial response; SD: stable disease; POD: progression of disease; PFS: progression free survival; OS: overall survival; AEs: adverse events; MPT: melphalan, prednisone, thalidomide; VMP: bortezomib, melphalan, prednisone; VTP: bortezomib, thalidomide, prednisone; Rd: lenalidomide, dexamethasone; VRd: bortezomib, lenalidomide, dexamethasone; CMP: carfilzomib, melphalan, prednisone; VMP-Rd: bortezomib, melphalan, prednisone - lenalidomide, dexamethasone; CyBorD(VCD): cyclophosphamide, bortezomib, dexamethasone; VMPT-VT: bortezomib, melphalan, prednisone - bortezomib, thalidomide; MPR: melphalan, prednisone, lenalidomide; MPT: melphalan, prednisone, lenalidomide; LFT: liver function tests; CHF: cardiac heart failure; Afib: atrial fibrillation; DVT: deep venous thrombosis; AKI: acute kidney injury; CNS: central nervous system.