Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts.
The international prognostic scoring system (IPSS) provides reliable risk assessment in patients with primary myelofibrosis (PMF). Recent clinical trials in PMF patients with intermediate-2 or high IPSS risk have shown a survival advantage of ruxolitinib over placebo (COMFORT-1) or best available therapy (COMFORT-2). Because crossover was allowed in these studies, we analyzed the cohort of ruxolitinib-naive patients used for developing the dynamic IPSS (DIPSS). By adopting ad hoc statistical analyses, we compared survival from diagnosis of 100 PMF patients receiving ruxolitinib within COMFORT-2 with that of 350 patients of the DIPSS study. Subjects were properly matched, and both left-truncation and right-censoring were accounted in order to compare higher IPSS risks exclusively. Patients receiving ruxolitinib had longer survival (5 years, 95% confidence interval [CI]: 2.9-7.8 vs 3.5 years, 95% CI: 3.0-3.9) with a hazard ratio of 0.61 (95% CI: 0.41-0.91; P = .0148). This observation suggests that ruxolitinib may modify the natural history of PMF.
Division of Hematology, Department of Medicine, University Hospital Ospedale di Circolo e Fondazione Macchi, Varese, Italy;
Francesco
F
Passamonti
Margherita
M
Maffioli
Francisco
F
Cervantes
Alessandro Maria
AM
Vannucchi
Enrica
E
Morra
Tiziano
T
Barbui
Domenica
D
Caramazza
Lisa
L
Pieri
Elisa
E
Rumi
Heinz
H
Gisslinger
Laurent
L
Knoops
Jean Jaques
JJ
Kiladjian
Barbara
B
Mora
Norbert
N
Hollaender
Cristiana
C
Pascutto
Claire
C
Harrison
Mario
M
Cazzola
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines
D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases