The Impact of Allogeneic Hematopoietic Cell Transplantation (HCT) and Treatment with Ruxolitinib on Survival in Patients with Myelofibrosis

Allogeneic HCT is curative in myelofibrosis (MF) with a survival (OS) advantage compared to non-JAK-inhibitor treatments in patients (pts) with Int-2/high-risk DIPSS (Kroeger et al, Blood 2015). On the other hand, data demonstrate a OS benefit of the JAK1/JAK2 inhibitor ruxolitinib (RUX) in intermediate (Int)-2/high-risk IPSS (Cervantes et al, Blood 2013; Verstovsek et al, Haematologica 2015 ) . Yet, comparative data to the impact of RUX and HCT on OS are lacking. This was pursued retrospectively at the University of Leipzig in light of clinical-, cytogenetic-, phenotype-driver-, and somatic mutations-based prognostic variables. Patient and Methods: RUX became available in November, 2009. MF pts (n=137; median age 58y) seen afterwards were included with the exception of MPL + pts (small number). Characteristics are shown in table 1. RUX was given for spleenomegaly and/or constitutional symptoms [n=76 (55%)]. Irrespective of RUX, a donor search was initiated in int-2 and high-risk IPSS pts Leukemia 2011. Somatic mutations detected by NGS were used to calculate molecular-risk (Vannucchi et al. Leukemia 2013). Results: Median OS time was 6.8 y. The RUX-group was older (median age 64 y) with profound spleenomegaly and a higher JAK2 V617F allele burden compared to the HCT group (median age 55 y) (p 50 y (p=0.001). In the RUX group, age 60 y (p=0.02)]. No prognostic implication of anemia, WBC, peripheral blasts, and constitutional symptoms could be detected with both treatments. OS in JAK2 + pts was similar to CALR + pts in both therapy cohorts (p=0.3). Triple negativity retained its detrimental influence (p ASXL1, EZH2) with splenomegaly(p=0.02),high-molecular epigenetic risk had no impact on OS or LT in the treatment groups. Unfavourable cytogenetics were associated with LT (p=0.04) but not OS in the two groups. Of the 24 pts with a LT, 15 (62%) received no RUX and no HCT. Conclusions: Our data imply that, besides allogeneic HCT, a prolonged JAK1/JAK2 inhibition could, at least partly, attenuate most of the prognostic detrimental parameters. Pre-treatment with ruxolitinib prior to HCT does not seem to have a negative impact on survival. It is the first time where outcome with a non-transplant procedure is shown to be comparable to that after HCT in MF, even in high-risk disease. This needs to be verified in prospective randomized trials to define the role of allogeneic HCT in the era of JAK1/JAK2 inhibition. Disclosures Roskos: Novartis: Honoraria. Al-Ali: Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.