Summary of the main characteristics and results of ruxolitinib studies in MF
| . | . | . | No. patients allocated . | Patients who discontinued (except deaths) . | Crossed over from control group to ruxolitinib (%) . | Median follow-up . | Mortality rate . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study . | Design . | Comparator . | Ruxolitinib . | Comparator . | Ruxolitinib (%) . | Comparator (%) . | Ruxolitinib . | Comparator . | Ruxolitinib (%) . | Comparator (%) . | HR (95% CI) . | P . | |
| COMFORT-I, planned cutoff7 | Phase 3 trial, randomized (1:1), blinded | Placebo | 155 | 154 | 12 (7.7) | 28 (18.1) | 36 (23.4) | 32 wk | 32 wk | 10 (6.4) | 14 (9.0) | ITT: 0.67 (0.30-1.50) | .83 |
| COMFORT-I, extended cutoff7 | — | — | — | — | — | — | — | 51 wk | 51 wk | 13 (8.4) | 24 (15.6) | ITT: 0.50 (0.25-0.98) | .04 |
| COMFORT-I, 2 y15 | — | — | — | — | 42 (27.1) | 43 (27.9) | 111 (72.1) | 103 wk | N/A | 27 (17.4) | 41 (26.6) | ITT: 0.58 (0.36-0.95) | .03 |
| COMFORT-I, 3 y16 | — | — | — | — | 63 (40.6) | 66 (42.8) | 111 (72.1) | 149 wk | N/A | 42 (27.1) | 54 (35.0) | ITT: 0.69 (0.46-1.03) | .07 |
| RPSFT: 0.36 (0.20-1.03) | N/A | ||||||||||||
| COMFORT-II, planned cutoff8 | Phase 3 trial, randomized (2:1), open (nonblinded) | BAT | 146 | 73 | 49 (33.5) | 38 (55.0)† | 18 (43) | 48 wk | 48 wk | 6 (4.1) | 4 (5.4) | ITT: 0.70 (0.20-2.39) | N/A |
| COMFORT-II, extended cutoff8 | — | — | — | — | — | — | — | — | — | 11 (7.5) | 4 (5.4) | ITT: 1.01 (0.32-3.24) | N/A |
| COMFORT-II, 3 y17 | — | — | — | — | 80 (54.8) | 22 (30) | 45 (61.6) | 151 wk | 122 wk | 29 (19.8) | 22 (30) | ITT: 0.48 (0.28-0.85) | .009 |
| COMFORT-II, 5 y18 | — | — | — | — | 107 (73) | 28 (38.3) | N/A | 4.5 y | 2.9 y | 59 (40.4) | 35 (47.9) | ITT: 0.67 (0.44-1.02) | .06 |
| RPSFT: 0.44 (0.18-1.04) | N/A | ||||||||||||
| Pooled COMFORT-I and II, 3 y14 | Placebo or BAT | 301 | 227 | 143 (47.5) | 127 (55.9) | 156 (68.7) | 34.3-34.7 mo | 71 (23.4) | 76 (33.5) | ITT: 0.65 (0.46-0.90 | .01 | ||
| RPSFT: 0.29 (0.13-0.63) | N/A | ||||||||||||
| Tefferi et al, 201126 | Case-control | Historical | 51* | 410‡ | 89% (at 3 y) | N/A | N/A | N/A | N/A | 18 (35) | N/A | N/A | .58 |
| Verstovsek et al, 201227 | Case-control | Historical | 107* | 310§ | 46% (at 3 y) | N/A | N/A | 32 mo | N/A | 33 (30.8) | 187 (60.3) | 0.58 (0.39-0.85) | .005 |
| Passamonti et al, 201428 | Case-control | Historical | 100‖ | 350¶ | N/A | N/A | N/A | 2.5 y# | 2.6 y# | 30 (30) | 258 (86) | 0.64 (0.40-0.96) | .034 |
| . | . | . | No. patients allocated . | Patients who discontinued (except deaths) . | Crossed over from control group to ruxolitinib (%) . | Median follow-up . | Mortality rate . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study . | Design . | Comparator . | Ruxolitinib . | Comparator . | Ruxolitinib (%) . | Comparator (%) . | Ruxolitinib . | Comparator . | Ruxolitinib (%) . | Comparator (%) . | HR (95% CI) . | P . | |
| COMFORT-I, planned cutoff7 | Phase 3 trial, randomized (1:1), blinded | Placebo | 155 | 154 | 12 (7.7) | 28 (18.1) | 36 (23.4) | 32 wk | 32 wk | 10 (6.4) | 14 (9.0) | ITT: 0.67 (0.30-1.50) | .83 |
| COMFORT-I, extended cutoff7 | — | — | — | — | — | — | — | 51 wk | 51 wk | 13 (8.4) | 24 (15.6) | ITT: 0.50 (0.25-0.98) | .04 |
| COMFORT-I, 2 y15 | — | — | — | — | 42 (27.1) | 43 (27.9) | 111 (72.1) | 103 wk | N/A | 27 (17.4) | 41 (26.6) | ITT: 0.58 (0.36-0.95) | .03 |
| COMFORT-I, 3 y16 | — | — | — | — | 63 (40.6) | 66 (42.8) | 111 (72.1) | 149 wk | N/A | 42 (27.1) | 54 (35.0) | ITT: 0.69 (0.46-1.03) | .07 |
| RPSFT: 0.36 (0.20-1.03) | N/A | ||||||||||||
| COMFORT-II, planned cutoff8 | Phase 3 trial, randomized (2:1), open (nonblinded) | BAT | 146 | 73 | 49 (33.5) | 38 (55.0)† | 18 (43) | 48 wk | 48 wk | 6 (4.1) | 4 (5.4) | ITT: 0.70 (0.20-2.39) | N/A |
| COMFORT-II, extended cutoff8 | — | — | — | — | — | — | — | — | — | 11 (7.5) | 4 (5.4) | ITT: 1.01 (0.32-3.24) | N/A |
| COMFORT-II, 3 y17 | — | — | — | — | 80 (54.8) | 22 (30) | 45 (61.6) | 151 wk | 122 wk | 29 (19.8) | 22 (30) | ITT: 0.48 (0.28-0.85) | .009 |
| COMFORT-II, 5 y18 | — | — | — | — | 107 (73) | 28 (38.3) | N/A | 4.5 y | 2.9 y | 59 (40.4) | 35 (47.9) | ITT: 0.67 (0.44-1.02) | .06 |
| RPSFT: 0.44 (0.18-1.04) | N/A | ||||||||||||
| Pooled COMFORT-I and II, 3 y14 | Placebo or BAT | 301 | 227 | 143 (47.5) | 127 (55.9) | 156 (68.7) | 34.3-34.7 mo | 71 (23.4) | 76 (33.5) | ITT: 0.65 (0.46-0.90 | .01 | ||
| RPSFT: 0.29 (0.13-0.63) | N/A | ||||||||||||
| Tefferi et al, 201126 | Case-control | Historical | 51* | 410‡ | 89% (at 3 y) | N/A | N/A | N/A | N/A | 18 (35) | N/A | N/A | .58 |
| Verstovsek et al, 201227 | Case-control | Historical | 107* | 310§ | 46% (at 3 y) | N/A | N/A | 32 mo | N/A | 33 (30.8) | 187 (60.3) | 0.58 (0.39-0.85) | .005 |
| Passamonti et al, 201428 | Case-control | Historical | 100‖ | 350¶ | N/A | N/A | N/A | 2.5 y# | 2.6 y# | 30 (30) | 258 (86) | 0.64 (0.40-0.96) | .034 |
N/A, not available in the original publication.
Patients from the phase I/II INCB18424-251 study6 treated at Mayo Clinic (Tefferi et al study) or the MD Anderson Medical Center (Verstovsek et al study).
Some patients kept being followed up in the extended phase of the study.
Patients selected from the historical series of the Mayo Clinic.
Patients selected from several historical series (MD Anderson, Pavia, Milan).
Patients with PMF from the COMFORT-II trial who were on ruxolitinib because either initially allocated or crossed over from the BAT arm.
Historical controls with IPSSS intermediate-2 or high-risk PMF, selected from the DIPSS series.
Because follow-up was left-truncated, the figures stand for the time at risk and not for the whole time on observation.