Ruxolitinib Is Under Investigation as JAK Inhibition Strategy for Multiple Myeloma

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 whether data existed for alternative JAK inhibitors in patients with multiple myeloma and which of those were being reviewed clinically.

Berenson explained that the only JAK inhibitor being evaluated in this setting is ruxolitinib (Jakafi), which his clinical team is currently evaluating. He noted that the drug was initially approved for treatment of patients with myelofibrosis, polycythemia vera, and graft-vs-host disease, but its indication has expanded to treat a plurality of disease states, including eczema, COVID-19 infection, and autoimmune diseases. Berenson concluded by highlighting that little research was conducted on JAK inhibitors for use in patients with myeloma before his team started evaluating ruxolitinib in that indication.

Topline data from a phase 1 study evaluating ruxolitinib combined with methylprednisolone for use in relapsed/refractory multiple myeloma found that the overall response rate (ORR) was 31% and clinical benefit rate was 34% with the 2-drug combination. Among 29 patients, 10 achieved at least a minor response, 12 had stable disease, and 7 patients had progressive disease. The median progression-free survival (PFS) was 3.5 months (range, 0.5-36.2) and the median duration of response (DOR) was 12.5 months (range, 2.8-36.2); the median time to response was 3.0 months.

For 20 patients who showed progressive disease, lenalidomide was added to the combination treatment. The overall response rate and clinical benefit rate was 30% and 40%, respectively. Within this group, 2 patients achieved a very good partial response, 4 had partial responses, 2 had minor responses, 8 had stable disease, and 4 had progressive disease. The median duration of response was not reached. The median time to response was 2.6 months (range, 0.7-15.0) and the median PFS was 3.5 months (range, 0.3-25.9) after adding lenalidomide.

Transcript:

Clinically, the only inhibitor that's been tried is by us, and that is the JAK inhibitor known as ruxolitinib. This drug was originally approved for people [with a JAK] mutation with myelofibrosis and then polycythemia vera, but the expansion of this drug is even moved into eczema, with commercials all over the Olympics for that drug. It has also been used to tamp down overactivity of patients who get COVID-19, and also with graft-vs-host disease for patients undergoing transplant—the cells from the donor knock out the host—and it is expanding.

These inhibitors are being used in a variety of autoimmune diseases, such as lupus, rheumatoid arthritis, inflammatory bowel diseases like Crohn's disease and ulcerative colitis, and even hair loss– alopecia areata. They are used as expanding in cancer, until we started using this [ruxolitinib] for myeloma, there really had been very little work done on it.

Reference

Berenson JR, Limon A, Rice S, et al. A phase I trial evaluating the addition of lenalidomide to patients with relapsed/refractory multiple myeloma progressing on ruxolitinib and methylprednisolone. Target Oncol. 2024;19(3):343-357. doi:10.1007/s11523-024-01049-w