Summary of benefits and limitations of maintenance therapy with novel drugs for clinical decision making
| Drug . | Dose/regimen . | Duration of therapy . | Impact on . | Risk groups . | Tolerance . | Level of evidence/rade of recommendation . | Comments . | ||
|---|---|---|---|---|---|---|---|---|---|
| Quality of response . | PFS . | OS . | |||||||
| Thalidomide | 50* (100) mg/d | Up to 1 y,† no correlation between duration and outcome‡ | Yes | Yes | Yes, preferentially if not part of the induction regimen; yes, in meta-analysis | No benefit In FISH defined high-risk patients§ Possible benefit in patients with abnormal metaphase cytogenetics and GEP-defined high risk | PNP, fatigue and other limiting dose and duration of therapy | I/A | Poor tolerance in some (particularly elderly) patients; not recommended for patients with FISH defined high-risk profile |
| Lenalidomide | 10‖ (5-15) mg/d continuously or days 1-21, every 28 d | Until PD or intolerance | Yes | Yes | Presently shown in one-third of studies | Does not overcome negative impact of FISH-defined unfavorable cytogenetics | Few discontinuations because of AEs | I/A | Unprecedented extension of PFS, increase in OS in 1 of 3 studies; usually well tolerated, increased risk for secondary primary malignancies |
| Bortezomib‖ | 1.3 mg biweekly | 2 y or until PD or intolerance | Yes¶ | Yes¶ | Yes¶ | Active in patients with renal failure and cytogenetic risk groups | PNP grades 3 or 4: 16% (based on intravenous administration) | Not applicable | Only comparison between PAD-ASCT bortezomib with VAD-ASCT thalidomide available |
| Bortezomib-thalidomide | GIMEMA: bortezomib-thalidomide yielded increased PFS vs control. PETHEMA: bortezomib-thalidomide resulted in a tendency for increased PFS vs VP. In both studies, an impact on OS was not observed. Results of ongoing trials need to be awaited. | ||||||||
| Drug . | Dose/regimen . | Duration of therapy . | Impact on . | Risk groups . | Tolerance . | Level of evidence/rade of recommendation . | Comments . | ||
|---|---|---|---|---|---|---|---|---|---|
| Quality of response . | PFS . | OS . | |||||||
| Thalidomide | 50* (100) mg/d | Up to 1 y,† no correlation between duration and outcome‡ | Yes | Yes | Yes, preferentially if not part of the induction regimen; yes, in meta-analysis | No benefit In FISH defined high-risk patients§ Possible benefit in patients with abnormal metaphase cytogenetics and GEP-defined high risk | PNP, fatigue and other limiting dose and duration of therapy | I/A | Poor tolerance in some (particularly elderly) patients; not recommended for patients with FISH defined high-risk profile |
| Lenalidomide | 10‖ (5-15) mg/d continuously or days 1-21, every 28 d | Until PD or intolerance | Yes | Yes | Presently shown in one-third of studies | Does not overcome negative impact of FISH-defined unfavorable cytogenetics | Few discontinuations because of AEs | I/A | Unprecedented extension of PFS, increase in OS in 1 of 3 studies; usually well tolerated, increased risk for secondary primary malignancies |
| Bortezomib‖ | 1.3 mg biweekly | 2 y or until PD or intolerance | Yes¶ | Yes¶ | Yes¶ | Active in patients with renal failure and cytogenetic risk groups | PNP grades 3 or 4: 16% (based on intravenous administration) | Not applicable | Only comparison between PAD-ASCT bortezomib with VAD-ASCT thalidomide available |
| Bortezomib-thalidomide | GIMEMA: bortezomib-thalidomide yielded increased PFS vs control. PETHEMA: bortezomib-thalidomide resulted in a tendency for increased PFS vs VP. In both studies, an impact on OS was not observed. Results of ongoing trials need to be awaited. | ||||||||
Lowest dose shown to be effective and therefore recommended; several studies used 100 mg or higher doses.
Spencer et al limited thalidomide therapy to 12 months.16
Barlogie et al.19
Morgan et al showed shortened survival in unfavorable FISH patients.17
Recommended starting dose; doses have been adapted to 5-15 mg in the CALGB study.
Different regimens during induction therapy limit comparability with the thalidomide maintenance arm.