Characteristics of the patients treated with first-line treatment
| . | Whole cohort . | TP53 wt . | High-burden TP53 mutation (≥10% VAF) . | Low-burden TP53 mutation (1-10% VAF) . | Low-burden TP53 mutation (<1% VAF) . | P* . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of patients | 511 | 370 (72) | 59 (12) | 29 (6) | 53 (10) | — | ||||
| Age at first-line treatment, median y (range) | 67.31 (35.0-94.0) | 66.8 (37.43-88.7) | 68.8 (35.1-81.3) | 67.6 (49.0-94.0) | 69.0 (41.6-81.1) | — | ||||
| Sex | — | |||||||||
| Female | 176 (34) | 120 (32) | 21 (36) | 12 (41) | 23 (43) | |||||
| Male | 335 (66) | 250 (68) | 38 (64) | 17 (59) | 30 (57) | |||||
| IGHV status† | Mut >10% vs wt; P = .003 | |||||||||
| Mutated | 142 (28) | 115 (32) | 6 (10) | 6 (21) | 15 (28) | |||||
| Unmutated | 362 (72) | 250 (68) | 52 (90) | 22 (79) | 38 (72) | |||||
| Discordant‡/NA | 4/3 | 3/2 | 0/1 | 1/0 | 0 | |||||
| FISH hierarchical§ | Del(17p) mut >10% vs all groups; P < .0001 | |||||||||
| Del(17p) | 41 (8) | 7 (2) | 34 (58) | 0 | 0 | |||||
| Del(11q) | 136 (27) | 108 (29) | 6 (10) | 6 (21) | 16 (30) | |||||
| +12 | 67 (13) | 56 (15) | 0 | 5 (17) | 6 (11) | |||||
| Del(13q) | 160 (31) | 116 (31) | 14 (24) | 12 (41) | 19 (36) | |||||
| Normal | 105 (21) | 82 (22) | 5 (8) | 6 (21) | 12 (23) | |||||
| NA | 2 | 2 | 0 | 0 | 0 | |||||
| CLL IPI | A | B | A | B | A | B | Not applicable | |||
| Low | 26 (6) | 26 (6) | 26 (8) | 0 | 0 | 0 | 0 | 0 | ||
| Intermediate | 102 (23) | 84 (19) | 84 (27) | 0 | 9 (36) | 0 | 9 (19) | 0 | ||
| High | 254 (57) | 203 (46) | 198 (63) | 2 (3) | 16 (64) | 2 (8) | 38 (81) | 1 (2) | ||
| Very high | 63 (14) | 132 (30) | 7 (2) | 56 (97) | 0 | 23 (92) | 0 | 46 (98) | ||
| NA | 66 | 55 | 1 | 4 | 6 | |||||
| TTFT, median mo (range) | 22.2 (0-246.6) | 24.2 (0-246.6) | 12.7 (0-127.6) | 18.1 (0-212.3) | 31.9 (0-168.3) | Mut >10% vs wt; P < .0001 and vs mut 1-10% P < 0.0001 | ||||
| First-line treatment | ||||||||||
| FCR | 263 (51) | 204 (55) | 17 (29) | 18 (62) | 24 (45) | FCR: mut>10% vs wt; P = .002; | ||||
| BR | 113 (22) | 89 (24) | 3 (5) | 6 (21) | 15 (28) | BR: mut >10% vs wt; P = .0005 | ||||
| Other|| | 135 (26) | 77 (21) | 39 (66) | 5 (17) | 14 (26) | Mut >10% vs mut <1%; P = .014 | ||||
| . | Whole cohort . | TP53 wt . | High-burden TP53 mutation (≥10% VAF) . | Low-burden TP53 mutation (1-10% VAF) . | Low-burden TP53 mutation (<1% VAF) . | P* . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of patients | 511 | 370 (72) | 59 (12) | 29 (6) | 53 (10) | — | ||||
| Age at first-line treatment, median y (range) | 67.31 (35.0-94.0) | 66.8 (37.43-88.7) | 68.8 (35.1-81.3) | 67.6 (49.0-94.0) | 69.0 (41.6-81.1) | — | ||||
| Sex | — | |||||||||
| Female | 176 (34) | 120 (32) | 21 (36) | 12 (41) | 23 (43) | |||||
| Male | 335 (66) | 250 (68) | 38 (64) | 17 (59) | 30 (57) | |||||
| IGHV status† | Mut >10% vs wt; P = .003 | |||||||||
| Mutated | 142 (28) | 115 (32) | 6 (10) | 6 (21) | 15 (28) | |||||
| Unmutated | 362 (72) | 250 (68) | 52 (90) | 22 (79) | 38 (72) | |||||
| Discordant‡/NA | 4/3 | 3/2 | 0/1 | 1/0 | 0 | |||||
| FISH hierarchical§ | Del(17p) mut >10% vs all groups; P < .0001 | |||||||||
| Del(17p) | 41 (8) | 7 (2) | 34 (58) | 0 | 0 | |||||
| Del(11q) | 136 (27) | 108 (29) | 6 (10) | 6 (21) | 16 (30) | |||||
| +12 | 67 (13) | 56 (15) | 0 | 5 (17) | 6 (11) | |||||
| Del(13q) | 160 (31) | 116 (31) | 14 (24) | 12 (41) | 19 (36) | |||||
| Normal | 105 (21) | 82 (22) | 5 (8) | 6 (21) | 12 (23) | |||||
| NA | 2 | 2 | 0 | 0 | 0 | |||||
| CLL IPI | A | B | A | B | A | B | Not applicable | |||
| Low | 26 (6) | 26 (6) | 26 (8) | 0 | 0 | 0 | 0 | 0 | ||
| Intermediate | 102 (23) | 84 (19) | 84 (27) | 0 | 9 (36) | 0 | 9 (19) | 0 | ||
| High | 254 (57) | 203 (46) | 198 (63) | 2 (3) | 16 (64) | 2 (8) | 38 (81) | 1 (2) | ||
| Very high | 63 (14) | 132 (30) | 7 (2) | 56 (97) | 0 | 23 (92) | 0 | 46 (98) | ||
| NA | 66 | 55 | 1 | 4 | 6 | |||||
| TTFT, median mo (range) | 22.2 (0-246.6) | 24.2 (0-246.6) | 12.7 (0-127.6) | 18.1 (0-212.3) | 31.9 (0-168.3) | Mut >10% vs wt; P < .0001 and vs mut 1-10% P < 0.0001 | ||||
| First-line treatment | ||||||||||
| FCR | 263 (51) | 204 (55) | 17 (29) | 18 (62) | 24 (45) | FCR: mut>10% vs wt; P = .002; | ||||
| BR | 113 (22) | 89 (24) | 3 (5) | 6 (21) | 15 (28) | BR: mut >10% vs wt; P = .0005 | ||||
| Other|| | 135 (26) | 77 (21) | 39 (66) | 5 (17) | 14 (26) | Mut >10% vs mut <1%; P = .014 | ||||
Data are number of patients (percentage of subgroup), unless otherwise indicated. CLL-IPI, according to International CLL-IPI Working Group.29 CLL-IPI A: TP53 mutations >10% VAF considered as TP53 defect. CLL-IPI B: All TP53 mutations, irrespective of VAF, considered as a TP53 defect.
NA, not available; TTFT, time to first treatment.
All groups were mutually compared. Only significant comparisons are shown.
Based on 98% identity threshold.
More than 1 clone with discordant mutational status detected.
According to Döhner et al.46
For complete list of treatment see supplemental Table 5.