Prognostic Factors For Outcome In Patients (pts) With Myelofibrosis (MF) Treated With Ruxolitinib (Rux)

Rux is a potent and specific oral JAK1 & 2 inhibitor that has demonstrated superiority over traditional therapies for the treatment of MF. In two phase 3 randomized studies, Rux demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life. In addition, Rux-treated pts demonstrated longer survival than those receiving placebo or best available therapy.

To assess prognostic factors for response and survival in pts with MF treated at MDACC with Rux.

The details of the study design have been previously published (Verstovsek et al. NEJM 2010;363:1117-1127): 107 consecutive pts were treated between 6/07 and 9/11 and thus were evaluable.

Median age was 66 years (range, 41-84), with 52% of pts being > 65 years. 66 pts (56%) had primary MF. By the International Prognostic Scoring System (IPSS) at the start of therapy, 10 (9%) had intermediate (int)-1, 34 (32%) int-2, and 63 (59%) high-risk MF. Karyotype was diploid in 59 (51%) pts. The JAK2V617F mutation was identified in 84 pts (78%) with a median allele burden of 65%. At baseline (BL), median spleen size was 19 cm (range, 0-36); 28 pts (26%) were RBC transfusion-dependent. Median BL platelets count was 277 x 10⁹/L (range, 100-1195). At BL, median hemoglobin was 10.3 g/dL (range, 7.2-16.9) and median WBC was 18 x 10⁹/L (range, 2.5-159): 65% of pts having WBC > 25 x 10⁹/L. 48 (45%) pts had peripheral blood blasts of >1%. Median follow-up was 47 months (mo; range, 2-72+). Rux was given for a median of 37 mo (range, 2-72+); 26 (24%) pts are still receiving Rux at the time of this analysis. Clinical improvement (defined as 50% reduction of spleen length per IWG) at any time was observed in 67 pts (63%) for a median of 40 mo (range 1-62+); 35 additional pts (33%) with post-BL assessments experienced a clinical benefit with noticeable reduction in spleen volume and improvement in symptoms. Only 3 pts had primary “refractory” disease and progressed while on Rux, and 2 pts were not evaluable for response. By univariate analysis, none of the BL pts’ characteristics was found to have a statistically significant effect on clinical improvement and clinical benefit. Nine pts (8%) experienced transformation into acute myeloid leukemia. Median overall survival (OS) and transformation-free survival (TFS) were 57 and 52 mo, respectively, while 3-year TFS and OS rates were 64% and 66%, respectively. By univariate analysis, higher platelets count, lower bone marrow blasts, and transfusion independency at BL were associated with better TFS. Similarly, higher platelets count, and transfusion independency were associated with better OS. By multivariate analysis, only higher platelets count, and transfusion independency at BL were positive independent prognostic factors for TFS and OS.

Even in the presence of poor disease characteristics, Rux provided significant clinical benefit in the great majority of pts with MF, including int-1 pts. Pts with low platelets counts and transfusion dependency at BL have suboptimal outcome. These poor prognostic factors could serve to advise pts of their prognosis and additional treatment options.

Off Label Use: Clofarabine use in AML. Cortes:Incyte: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding. Ravandi:Sunesis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Teva: Consultancy, Honoraria; Pfizer: Honoraria; Merck: Research Funding; Bayer/Onyx: Consultancy, Honoraria; EMD Serono: Research Funding; Medimmune: Research Funding; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Verstovsek:Incyte: Research Funding.