Responses in first-line JAK inhibitor randomized clinical trials
| Trial . | Key criteria . | Treatment . | N . | Baseline spleen volume (mL) . | SVR35 at week 24 . | TSS50 at week 24 . | Treatment response and survival . |
|---|---|---|---|---|---|---|---|
| COMFORT-1 | IPSS INT-2/HI Plt ≥100 | RUX | 155 | 2598 | 41.9% | 45.9% | Significantly prolonged OS with RUX: HR, 0.69 (95% CI, 0.50-0.96) SVR10 at week 24 associated with OS |
| Placebo | 154 | 2566 | 0.7% | 5.3% | |||
| COMFORT-2 | IPSS INT-2/HI Plt ≥100 | RUX | 146 | 2408 | 32% | NR | Nonsignificant prolonged OS with RUX: HR, 0.67 (95% CI, 0.44-1.02) |
| BAT∗ | 73 | 2318 | 0% | NR | |||
| JAKARTA | IPSS INT-2/HI Plt ≥50 | FED 400 mg | 96 | 2652 | 36% | 36% | No analysis of OS because of early closure |
| Placebo | 95 | 2660 | 1% | 7% | |||
| PERSIST-1 | IPSS INT-1/2/HI Any plt count | PAC 400 mg | 220 | 2006 | 19% | 19% | No difference in OS |
| BAT† | 106 | 2153 | 5% | 10% | |||
| SIMPLIFY-1 | IPSS INT-1/2/HI Plt ≥50 | MMB 200 mg | 215 | NR | 26.5% | 28.4% | OS similar with RUX and MMB TI at week 24 associated with prolonged OS (MMB) SVR35 at week 24 associated with prolonged OS (RUX) |
| RUX | 217 | NR | 29.0% | 42.2% | |||
| TRANSFORM-1 | DIPSS + INT-1/2/HI Plt ≥100 | RUX | 127 | 1639 | 31.5% | 41.7% | Study closed early due to failure to achieve TSS end point |
| RUX + NAV | 125 | 1441 | 63.2% | 39.2% | |||
| MANIFEST-2 | DIPSS INT-1/2/HI Plt ≥100 | RUX | 216 | 1383 | 35.2% | 46.3% | Study in progress |
| RUX + PELA | 214 | 1309 | 65.9% | 52.3% |
| Trial . | Key criteria . | Treatment . | N . | Baseline spleen volume (mL) . | SVR35 at week 24 . | TSS50 at week 24 . | Treatment response and survival . |
|---|---|---|---|---|---|---|---|
| COMFORT-1 | IPSS INT-2/HI Plt ≥100 | RUX | 155 | 2598 | 41.9% | 45.9% | Significantly prolonged OS with RUX: HR, 0.69 (95% CI, 0.50-0.96) SVR10 at week 24 associated with OS |
| Placebo | 154 | 2566 | 0.7% | 5.3% | |||
| COMFORT-2 | IPSS INT-2/HI Plt ≥100 | RUX | 146 | 2408 | 32% | NR | Nonsignificant prolonged OS with RUX: HR, 0.67 (95% CI, 0.44-1.02) |
| BAT∗ | 73 | 2318 | 0% | NR | |||
| JAKARTA | IPSS INT-2/HI Plt ≥50 | FED 400 mg | 96 | 2652 | 36% | 36% | No analysis of OS because of early closure |
| Placebo | 95 | 2660 | 1% | 7% | |||
| PERSIST-1 | IPSS INT-1/2/HI Any plt count | PAC 400 mg | 220 | 2006 | 19% | 19% | No difference in OS |
| BAT† | 106 | 2153 | 5% | 10% | |||
| SIMPLIFY-1 | IPSS INT-1/2/HI Plt ≥50 | MMB 200 mg | 215 | NR | 26.5% | 28.4% | OS similar with RUX and MMB TI at week 24 associated with prolonged OS (MMB) SVR35 at week 24 associated with prolonged OS (RUX) |
| RUX | 217 | NR | 29.0% | 42.2% | |||
| TRANSFORM-1 | DIPSS + INT-1/2/HI Plt ≥100 | RUX | 127 | 1639 | 31.5% | 41.7% | Study closed early due to failure to achieve TSS end point |
| RUX + NAV | 125 | 1441 | 63.2% | 39.2% | |||
| MANIFEST-2 | DIPSS INT-1/2/HI Plt ≥100 | RUX | 216 | 1383 | 35.2% | 46.3% | Study in progress |
| RUX + PELA | 214 | 1309 | 65.9% | 52.3% |
BAT, best available therapy; CI, confidence interval; DIPSS, dynamic IPSS; FED, fedratinib; HI, high; HR, hazard ratio; INT, intermediate; IPSS, International Prognostic Scoring System; MMB, momelotinib; NAV, navitoclax; NR, not reported; OS, overall survival; PELA, pelabresib; Plt, platelet; RUX, ruxolitinib.
BAT not including JAK inhibitors: 47% received hydroxyurea; 33% received no medication.
BAT not including JAK inhibitors: 57% received hydroxyurea.