MPN patients’ characteristics according to NFE2 mutational status
| . | All patients (n = 1243) . | All patients with NGS (n = 707) . | NFE2-mutated patients (n = 36) . | Non–NFE2-mutated patients (n = 671) . | P . |
|---|---|---|---|---|---|
| Age at MPN diagnosis, y, (median [IQR]) | 51 (40; 63) | 51 (40; 61) | 53 (44; 63) | 50.5 (39; 61) | .074 |
| Female, no. (%) | .170 | ||||
| No | 557 (44.81) | 311 (43.99) | 20 (55.56) | 291 (43.37) | |
| Yes | 686 (55.19) | 396 (56.01) | 16 (44.44) | 380 (56.63) | |
| MPN subtype, no. (%) | .359 | ||||
| ET | 577 (46.42) | 332 (46.96) | 12 (33.33) | 320 (47.69) | |
| PV | 411 (33.07) | 233 (32.96) | 17 (47.22) | 216 (32.19) | |
| PMF | 184 (14.8) | 113 (15.98) | 6 (16.67) | 107 (15.95) | |
| MDS/MPN | 12 (0.97) | 6 (0.85) | 0 | 6 (0.89) | |
| MPN unclassified | 59 (4.75) | 23 (3.25) | 1 (2.78) | 22 (3.28) | |
| Driver mutation, n (%) | .390 | ||||
| JAK2V617F | 909 (73.13) | 495 (70.01) | 29 (80.56) | 466 (69.45) | |
| JAK2 exon 12 | 7 (0.56) | 4 (0.57) | 0 | 4 (0.60) | |
| MPL | 41 (3.30) | 24 (3.39) | 2 (5.56) | 22 (3.28) | |
| CALR | 175 (14.08) | 116 (16.41) | 4 (11.11) | 112 (16.69) | |
| Triple negative | 105 (8.45) | 68 (9.62) | 1 (2.78) | 67 (9.99) | |
| Hgb, g/dL, median (IQR) | 14 (12.4; 15.8) | 13.7 (12.2; 15.7) | 15.15 (12.8; 16.2) | 13.7 (12.2; 15.6) | .274 |
| Ht, %, median (IQR) | 43.65 (39; 49) | 42.4 (38.1; 48.3) | 50 (43.5; 50.9) | 42.1 (38; 48) | .032 |
| Platelets, G/L, median (IQR) | 576 (344; 800) | 582 (341; 811) | 701 (350; 993) | 582 (338; 810) | .517 |
| WBC, G/L, median (IQR) | 9.4 (7.2; 12.5) | 9.5 (7.2; 12.9) | 10.48 (7.3; 12.5) | 9.5 (7.2; 12.9) | .941 |
| ANC, G/L, median (IQR) | 6.3 (4.6; 9.1) | 6.4 (4.7; 9.5) | 7.2 (3.3; 9.0) | 6.4 (4.7; 9.5) | .982 |
| Immature myeloid cells, no. (%) | .066 | ||||
| <2% | 1049 (84.39) | 591 (83.59) | 32 (88.89) | 559 (83.31) | |
| ≥2% | 84 (6.76) | 68 (9.62) | 0 | 68 (10.13) | |
| Circulating blasts, no. (%) | .396 | ||||
| No | 1098 (88.33) | 634 (89.67) | 32 (88.89) | 602 (89.72) | |
| ≥1% | 47 (3.78) | 33 (4.67) | 0 | 33 (4.92) | |
| Elevated LDH, no. (%) | .673 | ||||
| No | 159 (12.79) | 88 (12.45) | 2 (5.56) | 86 (12.82) | |
| Yes | 115 (9.25) | 82 (11.60) | 3 (8.33) | 79 (11.77) | |
| Performance status, no. (%) | .390 | ||||
| 0 | 339 (27.27) | 193 (27.30) | 4 (11.11) | 189 (28.17) | |
| 1 | 97 (7.80) | 79 (11.17) | 4 (11.11) | 75 (11.18) | |
| 2 | 15 (1.21) | 13 (1.84) | 0 | 13 (1.94) | |
| 3 | 1 (0.08) | 0 | 0 | 0 | |
| Constitutional symptoms, no. (%) | .232 | ||||
| No | 541 (43.52) | 301 (42.57) | 10 (27.78) | 291 (43.37) | |
| Yes | 76 (6.11) | 45 (6.36) | 3 (8.33) | 42 (6.26) | |
| Microvascular symptoms, no. (%) | .100 | ||||
| No | 463 (37.25) | 257 (36.35) | 8 (22.22) | 249 (37.11) | |
| Yes | 143 (11.50) | 77 (10.89) | 6 (16.67) | 71 (10.58) | |
| Splenomegaly, no. (%) | 1.00 | ||||
| No | 392 (31.54) | 235 (33.24) | 11 (30.56) | 224 (33.38) | |
| Yes | 297 (23.89) | 178 (25.18) | 9 (25) | 169 (25.19) | |
| RBC transfusion dependency, no. (%) | .549 | ||||
| No | 834 (67.10) | 478 (67.61) | 19 (52.78) | 459 (68.41) | |
| Yes | 28 (2.25) | 19 (2.69) | 1 (2.78) | 18 (2.68) | |
| No. of thrombotic events, median (IQR) | 0 (0; 1) | 0 (0; 1) | 0 (0; 1) | 0 (0; 1) | .444 |
| History of thrombotic events at diagnosis, no. (%) | 1.000 | ||||
| No | 871 (70.07) | 520 (73.55) | 27 (75) | 493 (73.47) | |
| Yes | 371 (29.85) | 186 (26.31) | 9 (25) | 177 (26.38) | |
| No. of hemorrhagic events, median (IQR) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | .751 |
| History of hemorrhagic events at diagnosis, no. (%) | .571 | ||||
| No | 1217 (97.91) | 691 (97.74) | 35 (97.22) | 656 (97.76) | |
| Yes | 26 (2.09) | 16 (2.26) | 1 (2.78) | 15 (2.24) | |
| Karyotype, no. (%) | .373 | ||||
| Normal | 89 (7.16) | 86 (12.16) | 8 (22.22) | 78 (11.62) | |
| Not normal excluding complex/monosomal | 45 (3.62) | 45 (6.36) | 2 (5.56) | 43 (6.41) | |
| Complex/monosomal | 8 (0.64) | 7 (0.99) | 1 (2.78) | 6 (0.89) | |
| No. of additional mutations, median (IQR) | 1 (0; 2) | 1 (0; 2) | 1 (0; 2) | 1 (0; 2) | .749 |
| TP53 mutation (%) | .712 | ||||
| No | 670 (53.90) | 670 (94.77) | 34 (94.44) | 636 (94.78) | |
| Yes | 37 (2.98) | 37 (5.23) | 2 (5.56) | 35 (5.22) | |
| HMR mutations (%) | .839 | ||||
| No | 544 (43.77) | 544 (76.94) | 27 (75) | 517 (77.05) | |
| Yes | 163 (13.11) | 163 (23.06) | 9 (25) | 154 (22.95) | |
| First-line cytoreductive treatment, no. (%) | .139 | ||||
| Hydroxyurea (HU) | 317 (80.46) | 23 (88.46) | 294 (79.89) | ||
| Interferon-α | 38 (9.64) | 0 | 38 (10.33) | ||
| Vercyte | 19 (4.82) | 1 (3.85) | 18 (4.89) | ||
| Anagrelide | 5 (1.27) | 0 | 5 (1.36) | ||
| Ruxolitinib or other JAK inhibitors | 13 (3.3) | 1 (3.85) | 12 (3.26) | ||
| Other treatment | 2 (0.51) | 1 (3.85) | 1 (0.27) | ||
| Hematological response to HU first line, no. (%) | .792 | ||||
| CR, CHR | 289 (91.17) | 21 (91.30) | 268 (91.16) | ||
| PR | 22 (6.94) | 2 (8.7) | 20 (6.8) | ||
| CI | 0 | 0 | 0 | ||
| SD | 6 (1.89) | 0 | 6 (2.04) | ||
| PD | 0 | 0 | 0 | ||
| Disease status at time of NFE2 diagnosis, no. (%) | NA | ||||
| Stable response | NA | NA | 22 (61.11) | NA | |
| Lost response | NA | NA | 14 (38.89) | NA | |
| No. of treatment lines at last FU, median (IQR) | 1 (1; 2) | 2 (1; 2.5) | 1 (1; 2) | .0016 | |
| Hematological response at last FU, no. (%) | .026 | ||||
| CR, CHR | 573 (46.10) | 345 (48.80) | 15 (41.67) | 330 (49.18) | |
| PR | 147 (11.83) | 63 (8.91) | 4 (11.11) | 59 (8.79) | |
| CI | 59 (4.75) | 25 (3.54) | 0 | 25 (3.73) | |
| SD | 152 (12.23) | 107 (15.13) | 9 (25) | 98 (14.61) | |
| PD | 87 (7) | 53 (7.50) | 8 (22.22) | 45 (6.71) | |
| AML/MDS transformation, no. (%) | 57 (4.63) | 38 (5.42) | 5 (13.89) | 33 (4.92) | .039 |
| . | All patients (n = 1243) . | All patients with NGS (n = 707) . | NFE2-mutated patients (n = 36) . | Non–NFE2-mutated patients (n = 671) . | P . |
|---|---|---|---|---|---|
| Age at MPN diagnosis, y, (median [IQR]) | 51 (40; 63) | 51 (40; 61) | 53 (44; 63) | 50.5 (39; 61) | .074 |
| Female, no. (%) | .170 | ||||
| No | 557 (44.81) | 311 (43.99) | 20 (55.56) | 291 (43.37) | |
| Yes | 686 (55.19) | 396 (56.01) | 16 (44.44) | 380 (56.63) | |
| MPN subtype, no. (%) | .359 | ||||
| ET | 577 (46.42) | 332 (46.96) | 12 (33.33) | 320 (47.69) | |
| PV | 411 (33.07) | 233 (32.96) | 17 (47.22) | 216 (32.19) | |
| PMF | 184 (14.8) | 113 (15.98) | 6 (16.67) | 107 (15.95) | |
| MDS/MPN | 12 (0.97) | 6 (0.85) | 0 | 6 (0.89) | |
| MPN unclassified | 59 (4.75) | 23 (3.25) | 1 (2.78) | 22 (3.28) | |
| Driver mutation, n (%) | .390 | ||||
| JAK2V617F | 909 (73.13) | 495 (70.01) | 29 (80.56) | 466 (69.45) | |
| JAK2 exon 12 | 7 (0.56) | 4 (0.57) | 0 | 4 (0.60) | |
| MPL | 41 (3.30) | 24 (3.39) | 2 (5.56) | 22 (3.28) | |
| CALR | 175 (14.08) | 116 (16.41) | 4 (11.11) | 112 (16.69) | |
| Triple negative | 105 (8.45) | 68 (9.62) | 1 (2.78) | 67 (9.99) | |
| Hgb, g/dL, median (IQR) | 14 (12.4; 15.8) | 13.7 (12.2; 15.7) | 15.15 (12.8; 16.2) | 13.7 (12.2; 15.6) | .274 |
| Ht, %, median (IQR) | 43.65 (39; 49) | 42.4 (38.1; 48.3) | 50 (43.5; 50.9) | 42.1 (38; 48) | .032 |
| Platelets, G/L, median (IQR) | 576 (344; 800) | 582 (341; 811) | 701 (350; 993) | 582 (338; 810) | .517 |
| WBC, G/L, median (IQR) | 9.4 (7.2; 12.5) | 9.5 (7.2; 12.9) | 10.48 (7.3; 12.5) | 9.5 (7.2; 12.9) | .941 |
| ANC, G/L, median (IQR) | 6.3 (4.6; 9.1) | 6.4 (4.7; 9.5) | 7.2 (3.3; 9.0) | 6.4 (4.7; 9.5) | .982 |
| Immature myeloid cells, no. (%) | .066 | ||||
| <2% | 1049 (84.39) | 591 (83.59) | 32 (88.89) | 559 (83.31) | |
| ≥2% | 84 (6.76) | 68 (9.62) | 0 | 68 (10.13) | |
| Circulating blasts, no. (%) | .396 | ||||
| No | 1098 (88.33) | 634 (89.67) | 32 (88.89) | 602 (89.72) | |
| ≥1% | 47 (3.78) | 33 (4.67) | 0 | 33 (4.92) | |
| Elevated LDH, no. (%) | .673 | ||||
| No | 159 (12.79) | 88 (12.45) | 2 (5.56) | 86 (12.82) | |
| Yes | 115 (9.25) | 82 (11.60) | 3 (8.33) | 79 (11.77) | |
| Performance status, no. (%) | .390 | ||||
| 0 | 339 (27.27) | 193 (27.30) | 4 (11.11) | 189 (28.17) | |
| 1 | 97 (7.80) | 79 (11.17) | 4 (11.11) | 75 (11.18) | |
| 2 | 15 (1.21) | 13 (1.84) | 0 | 13 (1.94) | |
| 3 | 1 (0.08) | 0 | 0 | 0 | |
| Constitutional symptoms, no. (%) | .232 | ||||
| No | 541 (43.52) | 301 (42.57) | 10 (27.78) | 291 (43.37) | |
| Yes | 76 (6.11) | 45 (6.36) | 3 (8.33) | 42 (6.26) | |
| Microvascular symptoms, no. (%) | .100 | ||||
| No | 463 (37.25) | 257 (36.35) | 8 (22.22) | 249 (37.11) | |
| Yes | 143 (11.50) | 77 (10.89) | 6 (16.67) | 71 (10.58) | |
| Splenomegaly, no. (%) | 1.00 | ||||
| No | 392 (31.54) | 235 (33.24) | 11 (30.56) | 224 (33.38) | |
| Yes | 297 (23.89) | 178 (25.18) | 9 (25) | 169 (25.19) | |
| RBC transfusion dependency, no. (%) | .549 | ||||
| No | 834 (67.10) | 478 (67.61) | 19 (52.78) | 459 (68.41) | |
| Yes | 28 (2.25) | 19 (2.69) | 1 (2.78) | 18 (2.68) | |
| No. of thrombotic events, median (IQR) | 0 (0; 1) | 0 (0; 1) | 0 (0; 1) | 0 (0; 1) | .444 |
| History of thrombotic events at diagnosis, no. (%) | 1.000 | ||||
| No | 871 (70.07) | 520 (73.55) | 27 (75) | 493 (73.47) | |
| Yes | 371 (29.85) | 186 (26.31) | 9 (25) | 177 (26.38) | |
| No. of hemorrhagic events, median (IQR) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | 0 (0; 0) | .751 |
| History of hemorrhagic events at diagnosis, no. (%) | .571 | ||||
| No | 1217 (97.91) | 691 (97.74) | 35 (97.22) | 656 (97.76) | |
| Yes | 26 (2.09) | 16 (2.26) | 1 (2.78) | 15 (2.24) | |
| Karyotype, no. (%) | .373 | ||||
| Normal | 89 (7.16) | 86 (12.16) | 8 (22.22) | 78 (11.62) | |
| Not normal excluding complex/monosomal | 45 (3.62) | 45 (6.36) | 2 (5.56) | 43 (6.41) | |
| Complex/monosomal | 8 (0.64) | 7 (0.99) | 1 (2.78) | 6 (0.89) | |
| No. of additional mutations, median (IQR) | 1 (0; 2) | 1 (0; 2) | 1 (0; 2) | 1 (0; 2) | .749 |
| TP53 mutation (%) | .712 | ||||
| No | 670 (53.90) | 670 (94.77) | 34 (94.44) | 636 (94.78) | |
| Yes | 37 (2.98) | 37 (5.23) | 2 (5.56) | 35 (5.22) | |
| HMR mutations (%) | .839 | ||||
| No | 544 (43.77) | 544 (76.94) | 27 (75) | 517 (77.05) | |
| Yes | 163 (13.11) | 163 (23.06) | 9 (25) | 154 (22.95) | |
| First-line cytoreductive treatment, no. (%) | .139 | ||||
| Hydroxyurea (HU) | 317 (80.46) | 23 (88.46) | 294 (79.89) | ||
| Interferon-α | 38 (9.64) | 0 | 38 (10.33) | ||
| Vercyte | 19 (4.82) | 1 (3.85) | 18 (4.89) | ||
| Anagrelide | 5 (1.27) | 0 | 5 (1.36) | ||
| Ruxolitinib or other JAK inhibitors | 13 (3.3) | 1 (3.85) | 12 (3.26) | ||
| Other treatment | 2 (0.51) | 1 (3.85) | 1 (0.27) | ||
| Hematological response to HU first line, no. (%) | .792 | ||||
| CR, CHR | 289 (91.17) | 21 (91.30) | 268 (91.16) | ||
| PR | 22 (6.94) | 2 (8.7) | 20 (6.8) | ||
| CI | 0 | 0 | 0 | ||
| SD | 6 (1.89) | 0 | 6 (2.04) | ||
| PD | 0 | 0 | 0 | ||
| Disease status at time of NFE2 diagnosis, no. (%) | NA | ||||
| Stable response | NA | NA | 22 (61.11) | NA | |
| Lost response | NA | NA | 14 (38.89) | NA | |
| No. of treatment lines at last FU, median (IQR) | 1 (1; 2) | 2 (1; 2.5) | 1 (1; 2) | .0016 | |
| Hematological response at last FU, no. (%) | .026 | ||||
| CR, CHR | 573 (46.10) | 345 (48.80) | 15 (41.67) | 330 (49.18) | |
| PR | 147 (11.83) | 63 (8.91) | 4 (11.11) | 59 (8.79) | |
| CI | 59 (4.75) | 25 (3.54) | 0 | 25 (3.73) | |
| SD | 152 (12.23) | 107 (15.13) | 9 (25) | 98 (14.61) | |
| PD | 87 (7) | 53 (7.50) | 8 (22.22) | 45 (6.71) | |
| AML/MDS transformation, no. (%) | 57 (4.63) | 38 (5.42) | 5 (13.89) | 33 (4.92) | .039 |
ANC, absolute neutrophil count; CI, clinical improvement; CHR, complete hematological remission; CR, complete remission; FU, follow-up; Hgb, hemoglobin; Ht, hematocrit; LDH, lactate dehydrogenase; NA, not applicable; PD, progressive disease; PR, partial response; RBC, red blood cells; SD, stable disease; WBC, white blood cells.