Table 1
Evaluated treatment sequences.
| Treatment sequences | |||
|---|---|---|---|
| First-line Tx; Data source | Second-line Tx; Probability of switching protocol; Data source | Third-line Tx Probability of switching protocol; Data source | Palliative Tx; Data source |
| MPT (19) | 1. VCD, 20% of cases (20) | 1. RD, 30% (22) | CP (24, 25) |
| 2. VD, 70% (21) | 2. BTP, 40% (23) | ||
| 3. RD, 10% (22) | 3. Chemo, 30% * | ||
| MPV (26) | 1. CTD, 90% (27) | 1. RD, 30% (22) | CP (24, 25) |
| 2. RD, 10% (22) | 2. BTP, 40% (23) | ||
| 3. Chemo, 30% * | |||
| CTD (28) | 1. MPV, 30% (29) | 1. RD, 30% (22) | CP (24, 25) |
| 2. VD, 60% (21) | 2. BTP, 40% | ||
| 3. RD, 10% (22) | 3. Chemo, 30%* | ||
| VCD (30) | 1. MPT (31) | 1. RD, 30% (22) | CP (24, 25) |
| 2. RD, 10% (22) | 2. BTP, 40% (23) | ||
| 3. Chemo, 30% * | |||
| BP (32) | 1. RD, 100% (22) | 1. BTP, 50% (23) | CP (24, 25) |
| 2. Chemo, 50% * | |||
Legend: B-bendamustine; C-cyclophosphamide; Chemo-standard chemotherapy; D-dexamethasone; M-melphalan; P-prednisone; R-lenalidomide; T-thalidomide; Tx-treatment; V-bortezomib;
* Chemotherapy included the following protocols: DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) (33, 34), DT-PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) (35, 36).
Patients switched from first-line treatment to different second- and third-line treatment options. The proportion of patients that switched to each particular protocol is presented in Table 1 (%). Data sources are referenced in parentheses.
Figure 1
Markov health states and state-to-state transitions. Legend: MT, maintenance treatment; Numbers 1, 2, and 3 indicate the treatment line.
Table 2
Discounted base-case analysis results.
| Strategy | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) |
|---|---|---|---|
| Starting with MPT | 116,500 | 3.70 | - |
| Starting with CTD | 123,400 | 3.41 | Dom |
| Starting with VCD | 126,700 | 3.99 | 35,300 |
| Starting with MPV | 163,300 | 4.76 | 47,200 |
| Starting with BP | 373,400 | 3.98 | Dom |
[i] Legend: BP, bendamustine, prednisone; CTD, cyclophosphamide, thalidomide, dexamethasone; Dom, dominated, ICER, incremental cost-effectiveness ratio; LY(s), life year(s); LYG, life year gained; MPT, melphalan, prednisone, thalidomide; MPV, melphalan, prednisone, bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; €, euro.
Table 3
Variation of annual discount rates.
| Discount rate → | 1.5% for effectiveness; 3% for costs | 5% for effectiveness and costs | ||||
|---|---|---|---|---|---|---|
| Strategy | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) |
| Starting with MPT | 116,500 | 3.85 | - | 110,500 | 3.51 | - |
| Starting with CTD | 123,400 | 3.53 | Dom | 117,900 | 3.25 | Dom |
| Starting with VCD | 126,700 | 4.16 | 32,500 | 121,800 | 3.77 | 43,800 |
| Starting with MPV | 163,300 | 5.01 | 43,100 | 156,100 | 4.47 | 49,600 |
| Starting with BP | 373,400 | 4.15 | Dom | 351,800 | 3.77 | Dom |
[i] Legend: BP, bendamustine, prednisone; CTD, cyclophosphamide, thalidomide, dexamethasone; Dom, dominated; Ext Dom, extended dominated; ICER, incremental cost-effectiveness ratio; LY(s), life year(s); LYG, life year gained; MPT, melphalan, prednisone, thalidomide; MPV, melphalan, prednisone, bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; €, euro
Figure 2
Sensitivity analysis - Cost-effectiveness plane. Sequences defined by the combinations of first- and second-line treatment. The thick line is the cost-effectiveness frontier.
Legend: BP, bendamustine, prednisone; CTD, cyclophosphamide, thalidomide, dexamethasone; ICER, incremental cost-effectiveness ratio; LY(s), life year(s); MPT, melphalan, prednisone, thalidomide; MPV, melphalan, prednisone, bortezomib; RD, lenalidomide, dexamethasone; VCD, bortezomib, cyclophosphamide, dexamethasone; VD, bortezomib, dexamethasone; €, euro.
Table 4
Sensitivity analysis results – varying probability of switching to the lenalidomide-based treatment options.
| Strategy | Without RD options | Probability of switching to RD increased by 20% | Probability of switching to RD increased by 50% | Probability of switching to RD increased by 100% (i.e., doubled) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cost (€) | Life expect-ancy (LYs) | ICER (€/LYG) | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) | |
| Starting with MPT | 73,000 | 3.63 | - | 124,700 | 3.71 | - | 137,400 | 3.73 | - | 160,300 | 3.77 | - |
| Starting with CTD | 76,900 | 3.29 | Dom | 132,800 | 3.43 | Dom | 147,300 | 3.47 | Dom | 174,200 | 3.54 | Dom |
| Starting with VCD | 82,800 | 3.89 | 36,900 | 136,400 | 4.00 | 39,800 | 151,400 | 4.03 | 46,500 | 178,800 | 4.09 | Ext Dom |
| Starting with MPV | 112,900 | 4.68 | 38,000 | 174,100 | 4.77 | 48,700 | 190,600 | 4.80 | 51,000 | 220,200 | 4.84 | 55,800 |
| Starting with BP* | 373,400 | 3.98 | Dom | 373,400 | 3.98 | Dom | 373,400 | 3.98 | Dom | 373,400 | 3.98 | Dom |
Legend: BP, bendamustine, prednisone; CTD, cyclophosphamide, thalidomide, dexamethasone; Dom, dominated; ICER, incremental cost-effectiveness ratio; LY(s), life year(s); LYG, life year gained; MPT, melphalan, prednisone, thalidomide; MPV, melphalan, prednisone, bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; €, euro
Table 5
Sensitivity analysis – ranking of the sequences when excluding the third-line chemotherapy.
| Strategy | Cost (€) | Life expectancy (LYs) | ICER (€/LYG) |
|---|---|---|---|
| Starting with MPT | 210,200 | 4.40 | - |
| Starting with CTD | 223,100 | 4.16 | Dom |
| Starting with VCD | 251,100 | 4.92 | Ext Dom |
| Starting with MPV | 266,000 | 5.53 | 55,800 |
| Starting with BP | 390,200 | 4.92 | Dom |
[i] Legend: BP, bendamustine, prednisone; CTD, cyclophosphamide, thalidomide, dexamethasone; Dom, dominated; Ext Dom, extended dominated; ICER, incremental cost-effectiveness ratio; LY(s), life year(s); MPT, melphalan, prednisone, thalidomide; MPV, melphalan, prednisone, bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; €, euro.