Dr McLornan on the Challenges of Identifying Optimal Timing for Transplantation in Myelofibrosis

“Where the future lies are the integration of those [JAK inhibitors and new agents] into conventional conditioning but also thinking about maintenance strategies because one of the biggest challenges is yes, we can identify the right patient for transplant and we can bring them through transplant, but unfortunately, 1 in 5 patients will relapse.”

Donal McLornan, MBBCh, MRCP, PhD, FRCPath, a consultant in hematology and stem cell transplantation at the University College London Hospitals NHS Foundation Trust, explained the ongoing challenge of identifying the optimal timing for patients with myelofibrosis to undergo allogeneic hematopoietic cell transplantation.

Historically, discussions about transplantation for patients with myelofibrosis have been centered on appropriate timing, McLornan began. In recent years, more available therapies, such as JAK inhibitors, have been integrated into the myelofibrosis treatment paradigm, he noted. Since 2011, the myelofibrosis landscape has seen 4 FDA approvals for JAK inhibitors, including ruxolitinib (Jakafi), fedratinib (Inrebic), pacritinib (Vonjo), and momelotinib (Ojjaara).

The management of myelofibrosis also depends on patients’ symptoms and spleen response, which include disease that is low-risk (asymptomatic), intermediate 1 (symptomatic and a bulky spleen), intermediate 2 (transplant eligible), and high- to very high–risk (not transplant eligible). Of note, patients with intermediate 1 and intermediate 2 disease could benefit most from receiving JAK inhibitors to maximize spleen and symptom response. Those with high- to very high–risk disease may also benefit from first-line JAK inhibitors to maximize spleen and symptom response and could continue to second-line JAK inhibitors if they have no response or lose response to first-line therapy.

However, with newer agents that have emerged, there is still a lot to learn about them, including the way these agents can modify the disease and how to best utilize them before, during, and after transplantation, he emphasized.

Considering the integration of these treatments into conventional conditioning, along with maintenance strategies, is where the future lies, McLornan explained. He added that identifying and selecting patients who would benefit from transplantation has been established. Nevertheless, 1 in 5 patients will relapse following transplantation, which is a significant challenge to navigate, he said. The future, with the prediction of outcome, will be the best integration of drugs, especially as a maintenance strategy post-transplantation, McLornan concluded.