The Prognostic Impact of the Mutational Profile in Patients with Myelofibrosis in the Era of the JAK1/JAK2-Inhibitor Ruxolitinib

• Published in: Blood 2014-12, Vol.124 (21), p.1860-1860
• Main Authors: Al-Ali, Haifa Kathrin, Wang, Song-Yau, Jaekel, Nadja, Koehler, Anne, Krahl, Rainer, Hubert, Karolin, Lange, Thoralf, Roskos, Martin, Stengel, Rayak, Kovacs, Ines, Scarlett, Schwabe, Schubert, Karoline, Wildenberger, Kathrin, Schneider, Melanie, Koehler, Elisabeth, Niederwieser, Dietger
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.1860.1860

In retrospective studies, CALR mutation is found to be a favorable prognostic variable in myelofibrosis (MF) compared with JAK2, or MPL mutations. With the availability of the JAK1/JAK2 inhibitor ruxolitinib (RUX) for treatment of MF, it is not yet known whether response varies across mutational subgroups and whether the prognostic implication of the driver mutations in terms of survival (OS) changes under RUX. We studied the prevalence and prognostic weight of clinical parameters in the IPSS and DIPSS-plus and the impact of RUX on OS in the context of mutation status. Patient and Methods: As of November 2009, RUX for treatment of splenomegaly and/or constitutional symptoms became an option at the University of Leipzig. All patients (pt) with MF seen since then were included (n=127; f=43%, median age 58 years) with the exception of pt with MPL mut+ because of small number. Screening for the JAK2V617F and CALR mutations was performed as previously published. Cytogenetic-risk categorization was conducted as published (Caramazza et al. Leukemia 2011). Results: JAK2 mut+ (group A; 60.6%) constituted the largest group, followed by CALR mut+ (group B; 19.7%), and “triple-negative” (group C; 19.7%). The median duration of MF was 22 months with no difference in the 3 groups. Higher-risk IPSS was present in the majority [Int-II 34.4%; high-risk 42.4%]. Constitutional symptoms were present across all groups, although more frequent in group A which was also characterized by prominent splenomegaly (Table). Group B pt were younger with low WBC in contrast to goup C pt who were older, anemic, with high WBC and low platelets, unfavorable cytogenetics and high-risk IPSS. Hb < 100 g/L (54%), and transfusion-dependency (32%) were frequently present in group B and was similar to group A. RUX was given to 72 (57%) pt [graoup A (66%), group B (56%), group C (29%)] with a median exposure of 8 months. The response of 80% was not influenced by the mutation status, cytogenetics, or IPSS variables. Leukemic transformation was documented in 22 pt [14 (64%) pt had no RUX exposure] after a median of 18 months after diagnosis. The incidence was highest in group C (36%) and lowest in group B (4%) (p=0.004). Unfavorable cytogenetics were 75%, and 27% in group C and A respectively. After a median follow-up of 31 months, OS at 3-years was 82% and worst in group C (72%) vs 80% for group A (p=0.05) vs 96% in goup B (p=0.003). In univariate analysis, non-mutated status (p=0.02), Int-2/high-ri