Myelofibrosis Treatment Advances Rely on Past Developments to Drive Future Innovation

Idoroenyi Amanam, MD

Future research in the field of myelofibrosis should address unanswered questions regarding the optimal roles for JAK inhibitor–based combination regimes, cellular therapy, and stem cell transplant, according to Idoroenyi Amanam, MD.

In an interview with OncLive^®, Amanam discussed the management of JAK inhibitor–associated adverse effects (AE) for patients with myelofibrosis, the shifting cellular therapy paradigm in this disease, and potential considerations for the future use of stem cell transplant.

He highlighted the roles of various available JAK inhibitors across myelofibrosis management and symptom control in another article.

Amanam is an assistant professor in the Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California.

OncLive: What are the common AEs associated with JAK inhibitors in myelofibrosis management? How do you manage these AEs in your practice?

Amanam: The most common AEs are cytopenias, especially for some patients with advanced myelofibrosis. Those are generally [the AEs that] I consider. Aside from cytopenias, I think about gastrointestinal [GI] toxicity. Cytopenias and GI toxicities are managed differently [from each other].

There is an expected level of cytopenia, especially when you initiate some of these drugs. What I would discuss with a patient up front is what I think may happen to their red blood cell, white blood cell, or platelet counts. Up front, the best option would be to be aware of this, but maybe not make any adjustments [at first]. However, if there continues to be a drop in the counts without a sustained benefit in the long term, we may need to make adjustments.

Regarding GI toxicities, for most patients, we manage those with anti-nausea medications or antidiarrheals. That is just symptomatic management.

What advancements in the management of myelofibrosis do you anticipate over the next few years?

Combination therapies with a JAK inhibitor plus another drug that targets proliferative signaling are of interest for all of us in this field. We're all patiently waiting and hoping to hear good news from the ASH Annual Meetings and the ASCO Annual Meetings. Aside from that, we are transitioning into an era where cellular therapy is of greater interest or consideration in this disease. I treat [patients with] myelofibrosis, but I also perform bone marrow transplants and allogeneic transplants.

Cellular therapy has been used for a long time to cure and relieve patients of the burden of myelofibrosis but we're investigating other ways to do that now. I am excited about how we're going to be transitioning with cellular therapy, continuing to identify new targets and proliferative signaling, [as well as] evaluating the microenvironment, in addition to [developing] other ways of using stem cell targets.

How might the use of stem cell transplant in this disease change going forward?

Importantly, we understand where stem cell transplant works in this disease better [than we used to]. Moving forward, it's going to be our job to do even better at selecting patients who may need to proceed with stem cell transplant earlier. It's going to get harder for us, with some of these newer drugs, to decide [when patients] should proceed with a newer therapy as opposed to sticking to what [we have been] doing. That's [a question] we're all trying to figure out; it hasn't been firm for us yet. We still have a lot to figure out, and I'm excited [about] where the field is headed.