OS from enrollment, showing bortezomib, dexamethasone, and thalidomide by protocol step
| OS with BSA-adjusted dosages . | OS without BSA-adjusted dosages . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Factor . | n/N (%) . | HR (95% CI) . | P . | HR (95% CI)* . | P* . | Factor . | HR (95% CI) . | P . | HR (95% CI)* . | P* . |
| Bortezomib during induction (mg/m2) | 303/303 (100) | 0.78 (0.66, 0.91) | .002 | 0.84 (0.72, 0.98) | .032 | Bortezomib during induction (mg) | 0.88 (0.81, 0.96) | .003 | 0.90 (0.84, 0.98) | .013 |
| Bortezomib during consolidation (mg/m2) | 232/303 (77) | 0.90 (0.83, 0.97) | .005 | 0.91 (0.85, 0.97) | .004 | Bortezomib during consolidation (mg) | 0.94 (0.90, 0.99) | .008 | 0.95 (0.91, 0.98) | .003 |
| Bortezomib during maintenance (mg/m2) | 215/303 (71) | 0.99 (0.97, 1.00) | .071 | 0.99 (0.97, 1.00) | .050 | Bortezomib during maintenance (mg) | 0.99 (0.98, 1.00) | .083 | 0.99 (0.98, 1.00) | .030 |
| Dexamethasone during induction (dg/m2) | 303/303 (100) | 0.62 (0.42, 0.92) | .017 | 0.71 (0.50, 1.02) | .066 | Dexamethasone during induction (dg) | 0.71 (0.56, 0.89) | .004 | 0.75 (0.60, 0.93) | .009 |
| Dexamethasone during transplant (dg/m2) | 260/303 (86) | 0.89 (0.74, 1.07) | .206 | 0.87 (0.74, 1.02) | .090 | Dexamethasone during transplant (dg) | 0.94 (0.84, 1.04) | .210 | 0.91 (0.83, 1.00) | .051 |
| Dexamethasone during consolidation (dg/m2) | 233/303 (77) | 0.75 (0.63, 0.89) | < .001 | 0.94 (0.83, 1.06) | .307 | Dexamethasone during consolidation (dg) | 0.85 (0.77, 0.93) | < .001 | 0.95 (0.89, 1.03) | .212 |
| Dexamethasone during maintenance (dg/m2) | 211/303 (70) | 0.88 (0.82, 0.94) | < .001 | 0.91 (0.86, 0.96) | .001 | Dexamethasone during maintenance (dg) | 0.93 (0.89, 0.97) | < .001 | 0.95 (0.92, 0.98) | .001 |
| Thalidomide during induction (g/m2) | 301/303 (99) | 0.52 (0.29, 0.94) | .031 | 0.62 (0.37, 1.05) | .075 | Thalidomide during induction (g) | 0.63 (0.44, 0.90) | .011 | 0.69 (0.50, 0.95) | .022 |
| Thalidomide during transplant (g/m2) | 253/303 (84) | 0.88 (0.77, 1.02) | .080 | 0.89 (0.79, 1.00) | .055 | Thalidomide during transplant (g) | 0.94 (0.87, 1.02) | .118 | 0.93 (0.87, 1.00) | .053 |
| Thalidomide during consolidation (g/m2) | 230/303 (76) | 0.89 (0.80, 0.99) | .036 | 0.95 (0.88, 1.03) | .231 | Thalidomide during consolidation (g) | 0.94 (0.89, 1.00) | .048 | 0.96 0.91, 1.00) | .073 |
| Thalidomide during maintenance (g/m2) | 195/303 (64) | 0.97 (0.94, 1.01) | .101 | 0.98 (0.96, 1.01) | .179 | Thalidomide during maintenance (g) | 0.98 (0.97, 1.00) | .094 | 0.99 (0.98, 1.00) | .155 |
| OS with BSA-adjusted dosages . | OS without BSA-adjusted dosages . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Factor . | n/N (%) . | HR (95% CI) . | P . | HR (95% CI)* . | P* . | Factor . | HR (95% CI) . | P . | HR (95% CI)* . | P* . |
| Bortezomib during induction (mg/m2) | 303/303 (100) | 0.78 (0.66, 0.91) | .002 | 0.84 (0.72, 0.98) | .032 | Bortezomib during induction (mg) | 0.88 (0.81, 0.96) | .003 | 0.90 (0.84, 0.98) | .013 |
| Bortezomib during consolidation (mg/m2) | 232/303 (77) | 0.90 (0.83, 0.97) | .005 | 0.91 (0.85, 0.97) | .004 | Bortezomib during consolidation (mg) | 0.94 (0.90, 0.99) | .008 | 0.95 (0.91, 0.98) | .003 |
| Bortezomib during maintenance (mg/m2) | 215/303 (71) | 0.99 (0.97, 1.00) | .071 | 0.99 (0.97, 1.00) | .050 | Bortezomib during maintenance (mg) | 0.99 (0.98, 1.00) | .083 | 0.99 (0.98, 1.00) | .030 |
| Dexamethasone during induction (dg/m2) | 303/303 (100) | 0.62 (0.42, 0.92) | .017 | 0.71 (0.50, 1.02) | .066 | Dexamethasone during induction (dg) | 0.71 (0.56, 0.89) | .004 | 0.75 (0.60, 0.93) | .009 |
| Dexamethasone during transplant (dg/m2) | 260/303 (86) | 0.89 (0.74, 1.07) | .206 | 0.87 (0.74, 1.02) | .090 | Dexamethasone during transplant (dg) | 0.94 (0.84, 1.04) | .210 | 0.91 (0.83, 1.00) | .051 |
| Dexamethasone during consolidation (dg/m2) | 233/303 (77) | 0.75 (0.63, 0.89) | < .001 | 0.94 (0.83, 1.06) | .307 | Dexamethasone during consolidation (dg) | 0.85 (0.77, 0.93) | < .001 | 0.95 (0.89, 1.03) | .212 |
| Dexamethasone during maintenance (dg/m2) | 211/303 (70) | 0.88 (0.82, 0.94) | < .001 | 0.91 (0.86, 0.96) | .001 | Dexamethasone during maintenance (dg) | 0.93 (0.89, 0.97) | < .001 | 0.95 (0.92, 0.98) | .001 |
| Thalidomide during induction (g/m2) | 301/303 (99) | 0.52 (0.29, 0.94) | .031 | 0.62 (0.37, 1.05) | .075 | Thalidomide during induction (g) | 0.63 (0.44, 0.90) | .011 | 0.69 (0.50, 0.95) | .022 |
| Thalidomide during transplant (g/m2) | 253/303 (84) | 0.88 (0.77, 1.02) | .080 | 0.89 (0.79, 1.00) | .055 | Thalidomide during transplant (g) | 0.94 (0.87, 1.02) | .118 | 0.93 (0.87, 1.00) | .053 |
| Thalidomide during consolidation (g/m2) | 230/303 (76) | 0.89 (0.80, 0.99) | .036 | 0.95 (0.88, 1.03) | .231 | Thalidomide during consolidation (g) | 0.94 (0.89, 1.00) | .048 | 0.96 0.91, 1.00) | .073 |
| Thalidomide during maintenance (g/m2) | 195/303 (64) | 0.97 (0.94, 1.01) | .101 | 0.98 (0.96, 1.01) | .179 | Thalidomide during maintenance (g) | 0.98 (0.97, 1.00) | .094 | 0.99 (0.98, 1.00) | .155 |
The univariate time-dependent models for OS fail to show a confounding effect of BSA on the cumulative dosing of bortezemib, dexamethasone, and thalidomide. Hazard ratio estimates are consistent after accounting for BSA within the original data and the data with updated follow-up.
OS indicates overall survival; n, number receiving a dose during the specified step; N, total number of patients on TT3 (2003-33); HR, hazard ratio; BSA, body surface area; and CI, confidence interval.
Data as of April 20, 2012.