The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo‐controlled, Phase III study in patients with myelofibrosis

Abstract

Summary Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100–200 × 109/l, >200 × 109/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan–Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.

A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis

“…9,10 There was no trend among the causes of death between men and women to account for the difference in survival observed; it is likely a composite of multiple factors that these studies were not specifically designed to evaluate. Although the above factors were shown to be prognostic in this analysis, a post hoc subgroup analysis of COMFORT-I 26 and a similar analysis of COMFORT-II 27 demonstrated that ruxolitinib treatment benefited each subgroup compared with placebo and BAT separately.…”

Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group

“…While this is likely appropriate in terms of therapeutic management, as supported also by the comparable efficacy of JAK2 inhibitors in subgroup analysis of patients treated with ruxolitinib [4,5] fedratinib [6], and pacritinib [7], it remains to be fully addressed whether the clinical course of secondary MF differs from PMF and which are the variables eventually influencing it. In particular as regards prognosis, there are evidences that the International Prognostic Score System (IPSS), that is routinely employed for both PMF and secondary MF, may not be performing satisfactorily in secondary forms of MF [8].…”

A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis

“…24 Long-term follow-up of COMFORT-1 patients recently presented by Verstovsek et al 25 continues to demonstrate an OS benefit in favor of ruxolitinib therapy after an additional year of observation (HR 5 0.58; 95% CI: 0.36, 0.95; P 5 .028) (Figure 1). This difference remained statistically significant across all MF subgroups, starting drug doses, baseline risk status, and hemoglobin level.…”

“…19 A planned additional data cutoff was also conducted after an additional 4-month followup period. At a median follow-up of 52 and 51 weeks, 13 (8.4%) BLOOD, 13 JUNE 2013 x VOLUME 121, NUMBER 24 …”