Ruxolitinib Elicits Few Adverse Effects When Treating Multiple Myeloma

CancerNetwork® spoke with James R. Berenson, MD, president and medical director of the Berenson Cancer Center, and founder of the Institute for Myeloma & Bone Cancer Research, about toxicities associated with ruxolitinib (Jakafi) combination therapy, as well as strategies for reducing them. Additionally, the synergistic effects of adding ruxolitinib to selinexor were discussed.

Berenson expressed that adverse effect (AE) occurrence with ruxolitinib was low. However, possible AEs observed with ruxolitinib included hematologic conditions and secondary cancer incidence. Highlighting ruxolitinib’s FDA approval history in other applications, Berenson stated that it was generally well tolerated and improved patient quality of life.

Berenson went on to spotlight greater AE incidence with selinexor, particularly for patients taking higher doses. He further explained that reducing its dosage and adding ruxolitinib reduced AE incidence and synergized them to attain better responses. Berenson concluded by speculating that the appetite-reducing properties of selinexor may be negated by the appetite-enhancing properties of ruxolitinib, before expressing that not enough clinical data was available to confirm that phenomenon.

Transcript:

[Adverse] effects from ruxolitinib are few and far between. Occasionally, patients can get some transient anemia several months [into treatment], and then it goes away. We have not seen much else. Overall, this drug can have a slight increase in the risk of blood clots like deep venous thrombosis and pulmonary emboli. There are data that suggest a higher risk of other cancers, specifically lymphoma, but those data are not very convincing in that regard. There may be some concern with secondary cancers and JAK inhibitors in general. Other than that, [ruxolitinib] is a well-tolerated oral [medicine] improving quality of life and a lot of other studies [evaluating ruxolitinib] have led to approvals by the FDA. It is pretty well tolerated.

Now, the other drug we are combining with [ruxolitinib is] selinexor and has a poor history, in that the initial doses were 80 mg twice a week, with lots of problems [including] low sodium, patients having [significant] anorexia, weight loss, nausea, vomiting, and poor blood counts [occurred]. We brought the dose down in this current trial to 40 mg. It is a whole different drug at those lower doses. The idea is, that when you combine 2 drugs, you can give both at lower doses, synergize them, get better responses, and– seeing that in the lab– hope to translate that in the clinic. We have 1 patient on [trial], and I will just smile, and that will tell you what is happening. We hope to expand this [significantly]. One of the cool things is that selinexor makes your appetite go away, especially at higher doses. On the other hand, ruxolitinib gives you the munchies and makes you want to eat. Together, it may be a good combination. Obviously, we do not have enough clinical data yet to say that for sure, though.