Early Results With Ruxolitinib-Based Treatment for Resistant Myeloma
Posted: Friday, May 22, 2020
In the lab, anti–multiple myeloma effects were achieved by combining the JAK inhibitor ruxolitinib with lenalidomide and dexamethasone; researchers believe that ruxolitinib blocks the expression of the oncoprotein MUC1, which, in turn, causes lenalidomide resistance in multiple myeloma cells. The results of their subsequent phase I study, published in Clinical Cancer Research, included a clinical benefit rate of nearly 50%. They propose that ruxolitinib may indeed restore sensitivity to lenalidomide in patients with relapsed or refractory myeloma.
The 28 enrolled patients had been treated with lenalidomide/steroids (to which 93% were refractory) and a proteasome inhibitor; they had experienced progressive disease at study entry after receiving a median of six prior treatments, noted Robert Vescio, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues. The primary study endpoints were to determine the treatment’s safety, as well as the patients’ clinical benefit rate and overall response rate. The patients, with a median age of 67 years, received ruxolitinib twice daily, lenalidomide daily on days 1 to 21 of a 28-day cycle, and methylprednisolone orally every other day. The trial used “a traditional 3+3 dose escalation design…, [and] no dose-limiting toxicities occurred.”
With rates of clinical benefit and overall response reported as 46% and 38%, respectively, the regimen seems to be a “promising novel therapeutic approach” for treating resistant myeloma, Dr. Vescio and co-investigators concluded. “Notably, all 12 responding patients were refractory to previous treatment with a lenalidomide- and steroid-containing combination.”
Adverse events of grade 3 or 4 included anemia (18%), thrombocytopenia (14%), and lymphopenia (14%). The most common serious adverse events included sepsis (11%) and pneumonia (11%).
Disclosure: The study authors’ disclosure information can be found at aacrjournals.org.