Ruxolitinib/Selinexor Combo Is Being Evaluated for Multiple Myeloma

Encouraging preclinical data foreground a clinical trial evaluating ruxolitinib (Jakafi) with selinexor (Xpovio) in patients with multiple myeloma, according to James R. Berenson, MD.

CancerNetwork® spoke with James R. Berenson, MD, founder, medical and scientific director, and president and chief executive officer of the Institute for Myeloma and Bone Cancer Research, and private practitioner in West Hollywood, California, about ongoing trials exploring JAK inhibitors in myeloma.

Berenson expressed that the first instance that ruxolitinib was used as a combination treatment for patients with JAK-mutated myeloma occurred when a patient with the mutation resisted lenalidomide (Revlimid) treatment. Upon the addition of ruxolitinib, treatment with lenalidomide began eliciting a response in the patient. This observance initiated clinical trials which showed that ruxolitinib displayed good activity with this patient group, and adding lenalidomide to patients who resisted ruxolitinib may initiate response as well.

The success of these trials spawned subsequent trials evaluating ruxolitinib with selinexor, which Berenson stated had exciting preclinical data. Berenson concluded by explaining that he expects data to be published from the trial evaluating ruxolitinib in combination with selinexor in 2025.

Transcript:

We started using JAK inhibitors in combination with lenalidomide and steroids in that […] the original reason for doing this was a case [where] a patient who had a JAK mutation and was being treated with ruxolitinib [Jakafi] and then tried a number of myeloma drugs without ruxolitinib and it did not work, but it was clear that resistance to lenalidomide, to which the patient had been on and failed without ruxolitinib, was really relying on a number of proteins that are driven by JAK. We figured that maybe inhibiting JAK may allow the lenalidomide to work again. Sure enough, that was the case.

That led into clinical trial and a lot of preclinical work. Clinical trials showed good success in about half of patients with this well-tolerated [oral] regimen. Then we started exploring the use of ruxolitinib alone without lenalidomide and found good activity. We also found that we could rescue patients who were [experiencing disease progression on ruxolitinib] by simply adding lenalidomide.

We have now moved into a series of newer trials, and excitingly, we are getting some interesting—in a good way—results with using [ruxolitinib] in combination with a medication called selinexor. This is a drug approved for myeloma that has not had a lot of use because the doses that were being used were pretty high and toxic. [W]ith very low doses, [selinexor], in combination with [ruxolitinib], has proven to be active among patients with myelofibrosis, and we are now moving it to myeloma.

Our preclinical data was exciting, and we are now off and running in the clinic, and stay tuned. We hopefully will have some data to report next year from the trial on this. It is a whole kind of new way to treat myeloma. It is very exciting.