How I treat transplant-eligible patients with myelofibrosis

In the most recent issue of Blood, Kröger et al elaborate on a practical treatment approach for allogeneic stem cell transplant (alloSCT)-eligible patients with myelofibrosis (MF) (1). We agree that pre-transplant spleen and symptom responses are important for post-transplant outcomes, and JAK-inhibition is the most useful way of achieving these. In addition, we want to emphasize the potential benefit of using second generation JAK-inhibitors. Our recent data of the prospective phase-II HOVON-134 trial, presented at the 2023 European Hematology Association conference, show feasibility of a pre-transplant induction with pacritinib, the novel and FDA-approved selective JAK2/IRAK1-inhibitor for MF patients (2). The treatment is of special interest in thrombocytopenic MF and even a relatively brief pre-transplant induction of 12-16 weeks of pacritinib at a 200 mg BID dose shows adequate responses and does not limit higher risk MF patients in proceeding to their intended alloSCT. Pacritinib shows a potential of additional response in ruxolitinib pre-treated and naïve patients in the pre-transplant setting. We hypothesize that this can be explained by its different kinome profile, as compared to other JAK-inhibitors, but also by the fact that ruxolitinib dosing might often be suboptimal due to side-effects and cytopenia. We have seen no primary graft failure and a low rate of secondary graft failure in this cohort after reduced-intensity conditioning and matched related or 10/10 matched unrelated donor alloSCT. These data add to the growing evidence for the use of JAK-inhibition before alloSCT in MF, and suggest additional benefits of using optimally dosed non-ruxolitinib JAK-inhibition in these patients.

Ruben Van Dijck, MD
Peter te Boekhorst, MD, PhD
Erasmus MC Cancer Institute, Rotterdam, The Netherlands

References:
(1)Kröger N, Wolschke C, Gagelmann N. How I treat transplant-eligible patients with myelofibrosis. Blood. 2023 Nov 16;142(20):1683-1696. doi: 10.1182/blood.2023021218. PMID: 37647853.
(2)Van Dijck R, van der Holt B, Broers A, Meijer E, Devos T, Hazenberg M, van der Poel M, Breems D, Deleu L, Kap M, van Hooije C, Cornelissen J, Schaap N, te Boekhorst P. Selective JAK2/IRAK1/ACVR1 inhitibor pacritinib before reduced-intensity conditioning allogeneic stem cell transplantation in myelofibrosis: final analysis of the phase-II HOVON-134 trial. EHA2021 Virtual Congress Abstract Book. HemaSphere 5():p e566, June 2021. | DOI: 10.1097/HS9.0000000000000566