According to an ongoing phase 1 trial, ruxolitinib in combination with steroids is a promising treatment option for heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM); these data were presented at the 63rd American Society of Hematology Annual Meeting.

“Preclinical studies from our laboratory have demonstrated that [ruxolitinib] in combination with dexamethasone shows marked anti-myeloma effects both in vitro and in vivo. Specifically, [ruxolitinib] blocks expression of Mucin 1 whose function is linked to lenalidomide resistance, downregulates PD-L1 and PD-L2 expression and reduces tumor stimulatory M2 macrophage polarization in multiple myeloma bone marrow,” explained James R. Berenson, MD, Berenson Cancer Center, West Hollywood, CA, and colleagues.

Following results from a phase 1 trial, in which heavily pretreated MM patients overcame refractoriness to lenalidomide and steroids when treated with ruxolitinib, lenalidomide, and methylprednisolone (Clin Cancer Res.), Dr Berenson and his team evaluated whether the combination of ruxolitinib and steroids without LEN was active for treating similar patients.

Using this two-drug combination, researchers treated a cohort within the current trial who have failed > 3 prior regimens and have previous exposure to a proteasome inhibitor and lenalidomide. Patients received 15 mg of oral ruxolitinib twice daily on days 1-28 of a 28-day cycle and 40 mg of methylprednisolone every other day until disease progression. After disease progression, patients were given 10 mg of oral lenalidomide daily on days 1-21 of a 28-day cycle. 

The primary endpoints were safety, objective response rate (ORR), and clinical benefit rate (CBR).

A total of 24 patients were enrolled, and the median number of prior treatments (including lenalidomide and steroid-containing regiments to which they were refractory) was 4 (range, 3-11). All but 1 patient have completed at least 1-full cycle of therapy and were evaluable for efficacy.

The median follow-up was 13 months, and median progression-free survival (PFS) was 4 months (range, 1-21). The ORR and CBR were 35% (9) and 39% (10), respectively; all 10 responding patients were refractory to lenalidomide. Of the remaining patients, 12 showed stable disease, and 4 had disease progression. Additionally, the median duration of response was 11 months (range, 1-20). Among the 13 patients who progressed on ruxolitinib and methylprednisolone and had lenalidomide added to their regimen, 6 responded (3 MR and 3 PR).

Nine patients experienced serious adverse events (SAEs), including sepsis (12%), sepsis with neutropenic fever (4%), thrombocytopenia (4%), hyperglycemia (4%), neutropenia (4%), anemia (4%), acute heart failure (4%), rotator cuff tear (4%), osteomyelitis (4%), aspiration pneumonia (4%), pneumonia and pneumothorax (4%), and deep venous thrombosis (4%); two patients died during this study (one of pneumonia and one from disease progression)

“This ongoing Phase 1 trial is the first study demonstrating clinical activity of the two-drug combination of the JAK inhibitor [ruxolitinib] with steroids for MM patients. The treatment was well tolerated and shows promising efficacy for treating heavily previously treated MM patients. Because of this, additional studies are being conducted with higher doses of [ruxolitinib] in combination with [methylprednisolone] for this patient population,” concluded Dr Berenson et al.—Alexandra Graziano

Berenson J, Martinez D, Safaie T, et al. Efficacy and Safety of Ruxolitinib and Steroids for Treating Patients with Relapsed or Refractory Multiple Myeloma. Presented at: the 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 2727.