Univariable and multivariable models for the difference in 3-y CNS relapse rates between i-HD-MTX and EOT groups, for all CNS relapses and for isolated CNS relapse only
| . | HR* (95% CI) . | 3-y difference, % (HR)† . | 3-y difference, %‡ . |
|---|---|---|---|
| All patients | |||
| EOT HD-MTX (UVA) | 1.01 (0.65-1.57) | 0.04 (−2.0 to 3.1) | 0.06 (−2.63 to 2.76) |
| EOT HD-MTX (adjusted§) | 1.06 (0.67-1.66) | 0.3 (−1.8 to 3.6) | 0.79 (−1.95 to 3.52) |
| EOT HD-MTX (adjustedǁ) | 0.07 (−2.59 to 2.73) | ||
| Landmark cohort only | |||
| EOT HD-MTX (UVA) | 0.99 (0.60-1.66) | −0.03 (−1.0 to 3.0%) | 0.02 (−2.58 to 2.63) |
| EOT HD-MTX (adjusted§) | 0.96 (0.55-1.67) | −0.2 (−2.1 to 3.0%) | 0.47 (−2.18 to 3.12) |
| EOT HD-MTX (adjustedǁ) | −0.11 (−2.70 to 2.48) | ||
| Isolated CNS relapse | |||
| EOT HD-MTX (UVA) | 1.07 (0.63-1.81) | 0.3 (−1.4 to 3.0%) | 0.47 (−1.84 to 2.78) |
| EOT HD-MTX (adjusted§) | 1.10 (0.64-1.87) | 0.4 (−1.4 to 3.2) | 1.00 (−1.38 to 3.30) |
| EOT HD-MTX (adjustedǁ) | 0.33 (−2.00 to 2.63) | ||
| Isolated CNS relapse, landmark cohort | |||
| EOT HD-MTX (UVA) | 1.07 (0.60-1.93) | 0.2 (−1.3 to 2.9%) | 1.11 (−1.34 to 3.56) |
| EOT HD-MTX (adjusted§) | 1.05 (0.57-1.95) | 0.2 (−1.7 to 3.6) | 1.02 (−1.33 to 3.37) |
| EOT HD-MTX (adjustedǁ) | 0.93 (−1.51 to 3.36) |
| . | HR* (95% CI) . | 3-y difference, % (HR)† . | 3-y difference, %‡ . |
|---|---|---|---|
| All patients | |||
| EOT HD-MTX (UVA) | 1.01 (0.65-1.57) | 0.04 (−2.0 to 3.1) | 0.06 (−2.63 to 2.76) |
| EOT HD-MTX (adjusted§) | 1.06 (0.67-1.66) | 0.3 (−1.8 to 3.6) | 0.79 (−1.95 to 3.52) |
| EOT HD-MTX (adjustedǁ) | 0.07 (−2.59 to 2.73) | ||
| Landmark cohort only | |||
| EOT HD-MTX (UVA) | 0.99 (0.60-1.66) | −0.03 (−1.0 to 3.0%) | 0.02 (−2.58 to 2.63) |
| EOT HD-MTX (adjusted§) | 0.96 (0.55-1.67) | −0.2 (−2.1 to 3.0%) | 0.47 (−2.18 to 3.12) |
| EOT HD-MTX (adjustedǁ) | −0.11 (−2.70 to 2.48) | ||
| Isolated CNS relapse | |||
| EOT HD-MTX (UVA) | 1.07 (0.63-1.81) | 0.3 (−1.4 to 3.0%) | 0.47 (−1.84 to 2.78) |
| EOT HD-MTX (adjusted§) | 1.10 (0.64-1.87) | 0.4 (−1.4 to 3.2) | 1.00 (−1.38 to 3.30) |
| EOT HD-MTX (adjustedǁ) | 0.33 (−2.00 to 2.63) | ||
| Isolated CNS relapse, landmark cohort | |||
| EOT HD-MTX (UVA) | 1.07 (0.60-1.93) | 0.2 (−1.3 to 2.9%) | 1.11 (−1.34 to 3.56) |
| EOT HD-MTX (adjusted§) | 1.05 (0.57-1.95) | 0.2 (−1.7 to 3.6) | 1.02 (−1.33 to 3.37) |
| EOT HD-MTX (adjustedǁ) | 0.93 (−1.51 to 3.36) |
The 10-y cut off for lifetime lost was chosen as close to the end of follow-up (131 mo, and after the last event).
CNS, central nervous system; ECOG, Eastern Cooperative Group performance status; EOT, end of treatment; HD-MTX, high-dose methotrexate; HR, hazard ratio; i-HD-MTX, intercalated high-dose methotrexate; IT, intrathecal; LDH, lactate dehydrogenase; UVA, univariate analysis.
HR for EOT vs i-HD-MTX.
Calculated by applying the hazard ratio to the 3-y rate in the i-HD-MTX group to get the corresponding rate in the EOT group, and then taking the difference.
Difference in cumulative incidence rates allowing for competing risks at 3 y using pseudo-observations.
Full model adjusted for sex, age, advanced stage, extra nodal disease (≥2 sites), ECOG (≥2), renal/adrenal involvement, raised LDH (plus ITs, HDMTX ≥2 doses, and cumulative dose >6 g/m2 for landmark cohort).
Adjusted for only variables significant with backward selection (based on survival time lost): age and renal/adrenal involvement for CNS relapse and age alone for isolated CNS relapse.