Univariate Cox proportional hazard analysis of OS and PFS in the LRF CLL4 patients
| . | Mutation/Biomarkers . | . | Overall Survival (mouths) . | Progression-free survival (months) . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total . | Events . | Median . | 95% CI . | HR . | 95% CI . | P . | Total . | Events . | Median (mean) . | 95% CI . | HR . | 95% CI . | P . | |||
| Gene mutation | NOTCH1 | Wild-type | 420 | 308 | 74.6 | 68.4-80.9 | 420 | 387 | 26.4 | 23.6-29.3 | ||||||
| Mutated | 46 | 40 | 54.8 | 31.0-78.5 | 1.47 | 1.06-2.05 | .02 | 46 | 45 | 22.0 | 17.2-26.9 | 1.46 | 1.07-1.99 | .02 | ||
| SF3B1 | Wild-type | 364 | 250 | 79.0 | 71.8-86.3 | 364 | 326 | 26.5 (39.1) | 23.1-29.9 | |||||||
| Mutated | 73 | 66 | 54.3 | 47.3-61.4 | 1.71 | 1.30-2.25 | < .001 | 73 | 73 | 26.5 (29.4) | 22.4-30.7 | 1.32 | 1.02-1.71 | .03 | ||
| Clinical feature | Age | 1.05 | 1.04-1.07 | < .001 | 1.00 | 0.99-1.01 | .87 | |||||||||
| Sex | Male | 365 | 280 | 70.3 | 61.4-79.2 | 365 | 340 | 25.2 | 22.3-28.2 | |||||||
| Female | 129 | 86 | 79.7 | 66.5-93.0 | 0.77 | 0.61-0.98 | .04 | 129 | 115 | 29.4 | 25.5-33.3 | 0.79 | 0.64-0.98 | .03 | ||
| Binet Stage (A/B/C) | A | 112 | 76 | 80.6 | 63.4-97.7 | 112 | 104 | 27.2 | 23.8-30.7 | |||||||
| B | 231 | 174 | 76.7 | 70.2-83.3 | 231 | 213 | 26.5 | 22.5-30.6 | ||||||||
| C | 151 | 116 | 54.3 | 44.8-63.8 | 1.21 | 1.04-1.39 | .01 | 151 | 138 | 24.4 | 18.4-30.4 | 1.02 | 0.89-1.16 | .77 | ||
| Binet Stage (A vs. B/C) | A | 112 | 76 | 80.6 | 63.4-97.7 | 112 | 104 | 27.2 | 23.8-30.7 | |||||||
| B/C | 382 | 290 | 71.5 | 64.8-78.2 | 1.29 | 1.01-1.67 | .04 | 382 | 351 | 26.1 | 23.0-29.1 | 1.00 | 0.81-1.25 | .98 | ||
| Biomarker | IGHV status | Mutated | 115 | 91 | 104.2 | 93.3-115.1 | 115 | 128 | 34.8 | 29.3-40.4 | ||||||
| Unmutated | 254 | 215 | 60.6 | 52.5-68.7 | 2.18 | 1.70-2.79 | < .001 | 254 | 249 | 22.7 | 20.2-25.2 | 1.86 | 1.49-2.31 | < .001 | ||
| ZAP70 positive | Negative | 177 | 117 | 84.7 | 69.6-99.8 | 177 | 154 | 30.5 | 25.5-35.4 | |||||||
| Positive | 197 | 162 | 69.0 | 59.7-78.2 | 1.47 | 1.16-1.86 | .002 | 197 | 188 | 23.0 | 20.2-25.8 | 1.42 | 1.15-1.76 | .001 | ||
| CD38 positive | Negative | 223 | 149 | 84.7 | 73.8-95.6 | 223 | 199 | 28.5 | 24.4-32.7 | |||||||
| Positive | 177 | 145 | 64.5 | 54.2-74.9 | 1.54 | 1.22-1.94 | < .001 | 177 | 169 | 21.6 | 17.6-25.7 | 1.39 | 1.13-1.70 | .002 | ||
| TP53 del/mut | Normal | 431 | 313 | 75.9 | 69.7-82.1 | 431 | 395 | 26.7 | 23.9-29.5 | |||||||
| Del/mut | 32 | 31 | 26.1 | 4.9-47.3 | 3.19 | 2.20-4.62 | < .001 | 32 | 32 | 3.9 | 0.57-7.3 | 2.70 | 1.88-3.89 | < .001 | ||
| del(11q) | Undeleted | 372 | 266 | 75.0 | 67.5-82.6 | 372 | 340 | 28.5 | 26.0-31.0 | |||||||
| Deleted | 92 | 79 | 57.7 | 42.4-73.0 | 1.62 | 1.26-2.09 | < .001 | 92 | 88 | 17.9 | 13.4-22.5 | 1.49 | 1.18-1.88 | .001 | ||
| del(13q)sole | Undeleted | 284 | 227 | 58.4 | 48.7-68.1 | 284 | 270 | 23.0 | 20.6-25.4 | |||||||
| Deleted | 177 | 115 | 88.9 | 73.2-104.5 | 0.59 | 0.47-0.74 | < .001 | 177 | 155 | 32.3 | 28.0-36.5 | 0.67 | 0.56-84.0 | < .001 | ||
| Trisomy12 | Absent | 388 | 284 | 73.9 | 67.3-80.4 | 388 | 357 | 26.5 | 23.5-29.5 | |||||||
| Present | 76 | 61 | 59.4 | 38.9-80.1 | 1.30 | 0.98-1.71 | .07 | 76 | 71 | 19.4 | 11.9-26.8 | 1.28 | 0.99-1.65 | .06 | ||
| . | Mutation/Biomarkers . | . | Overall Survival (mouths) . | Progression-free survival (months) . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total . | Events . | Median . | 95% CI . | HR . | 95% CI . | P . | Total . | Events . | Median (mean) . | 95% CI . | HR . | 95% CI . | P . | |||
| Gene mutation | NOTCH1 | Wild-type | 420 | 308 | 74.6 | 68.4-80.9 | 420 | 387 | 26.4 | 23.6-29.3 | ||||||
| Mutated | 46 | 40 | 54.8 | 31.0-78.5 | 1.47 | 1.06-2.05 | .02 | 46 | 45 | 22.0 | 17.2-26.9 | 1.46 | 1.07-1.99 | .02 | ||
| SF3B1 | Wild-type | 364 | 250 | 79.0 | 71.8-86.3 | 364 | 326 | 26.5 (39.1) | 23.1-29.9 | |||||||
| Mutated | 73 | 66 | 54.3 | 47.3-61.4 | 1.71 | 1.30-2.25 | < .001 | 73 | 73 | 26.5 (29.4) | 22.4-30.7 | 1.32 | 1.02-1.71 | .03 | ||
| Clinical feature | Age | 1.05 | 1.04-1.07 | < .001 | 1.00 | 0.99-1.01 | .87 | |||||||||
| Sex | Male | 365 | 280 | 70.3 | 61.4-79.2 | 365 | 340 | 25.2 | 22.3-28.2 | |||||||
| Female | 129 | 86 | 79.7 | 66.5-93.0 | 0.77 | 0.61-0.98 | .04 | 129 | 115 | 29.4 | 25.5-33.3 | 0.79 | 0.64-0.98 | .03 | ||
| Binet Stage (A/B/C) | A | 112 | 76 | 80.6 | 63.4-97.7 | 112 | 104 | 27.2 | 23.8-30.7 | |||||||
| B | 231 | 174 | 76.7 | 70.2-83.3 | 231 | 213 | 26.5 | 22.5-30.6 | ||||||||
| C | 151 | 116 | 54.3 | 44.8-63.8 | 1.21 | 1.04-1.39 | .01 | 151 | 138 | 24.4 | 18.4-30.4 | 1.02 | 0.89-1.16 | .77 | ||
| Binet Stage (A vs. B/C) | A | 112 | 76 | 80.6 | 63.4-97.7 | 112 | 104 | 27.2 | 23.8-30.7 | |||||||
| B/C | 382 | 290 | 71.5 | 64.8-78.2 | 1.29 | 1.01-1.67 | .04 | 382 | 351 | 26.1 | 23.0-29.1 | 1.00 | 0.81-1.25 | .98 | ||
| Biomarker | IGHV status | Mutated | 115 | 91 | 104.2 | 93.3-115.1 | 115 | 128 | 34.8 | 29.3-40.4 | ||||||
| Unmutated | 254 | 215 | 60.6 | 52.5-68.7 | 2.18 | 1.70-2.79 | < .001 | 254 | 249 | 22.7 | 20.2-25.2 | 1.86 | 1.49-2.31 | < .001 | ||
| ZAP70 positive | Negative | 177 | 117 | 84.7 | 69.6-99.8 | 177 | 154 | 30.5 | 25.5-35.4 | |||||||
| Positive | 197 | 162 | 69.0 | 59.7-78.2 | 1.47 | 1.16-1.86 | .002 | 197 | 188 | 23.0 | 20.2-25.8 | 1.42 | 1.15-1.76 | .001 | ||
| CD38 positive | Negative | 223 | 149 | 84.7 | 73.8-95.6 | 223 | 199 | 28.5 | 24.4-32.7 | |||||||
| Positive | 177 | 145 | 64.5 | 54.2-74.9 | 1.54 | 1.22-1.94 | < .001 | 177 | 169 | 21.6 | 17.6-25.7 | 1.39 | 1.13-1.70 | .002 | ||
| TP53 del/mut | Normal | 431 | 313 | 75.9 | 69.7-82.1 | 431 | 395 | 26.7 | 23.9-29.5 | |||||||
| Del/mut | 32 | 31 | 26.1 | 4.9-47.3 | 3.19 | 2.20-4.62 | < .001 | 32 | 32 | 3.9 | 0.57-7.3 | 2.70 | 1.88-3.89 | < .001 | ||
| del(11q) | Undeleted | 372 | 266 | 75.0 | 67.5-82.6 | 372 | 340 | 28.5 | 26.0-31.0 | |||||||
| Deleted | 92 | 79 | 57.7 | 42.4-73.0 | 1.62 | 1.26-2.09 | < .001 | 92 | 88 | 17.9 | 13.4-22.5 | 1.49 | 1.18-1.88 | .001 | ||
| del(13q)sole | Undeleted | 284 | 227 | 58.4 | 48.7-68.1 | 284 | 270 | 23.0 | 20.6-25.4 | |||||||
| Deleted | 177 | 115 | 88.9 | 73.2-104.5 | 0.59 | 0.47-0.74 | < .001 | 177 | 155 | 32.3 | 28.0-36.5 | 0.67 | 0.56-84.0 | < .001 | ||
| Trisomy12 | Absent | 388 | 284 | 73.9 | 67.3-80.4 | 388 | 357 | 26.5 | 23.5-29.5 | |||||||
| Present | 76 | 61 | 59.4 | 38.9-80.1 | 1.30 | 0.98-1.71 | .07 | 76 | 71 | 19.4 | 11.9-26.8 | 1.28 | 0.99-1.65 | .06 | ||
The double SF3B1 mutated (700 and 742) cases (n = 2) remain in this analysis. We performed the analysis excluding these cases and obtained similar results. TP53 abnormalities defined by deletion and/or mutation (del/mut).