Jakafi Plus Steroid Continuing to Treat Multiple Myeloma in Phase 1 Trial

Combining the corticosteroid methylprednisolone and Jakafi (ruxolitinib), an approved oral therapy for bone marrow disorders, is showing promising effectiveness in heavily pre-treated multiple myeloma patients in an ongoing Phase 1 trial.

Findings to date from this open-label study (NCT03110822), which is being sponsored by Onco Therapeutics, showed that the combination not only elicited promising responses but was also capable of restoring sensitivity to Revlimid (lenalidomide), an approved immunomodulatory agent.

“Besides having a direct MM [multiple myeloma] killing effect, ruxolitinib’s ability to resensitize lenalidomide is a major advantage that allows clinicians to recycle drugs and recapture disease control, while maintaining the convenience of an all-oral regimen. This is an entirely new treatment approach for MM patients,” James Berenson, MD, president of the clinical research organization Onco Therapeutics and the trial’s lead investigator, said in a press release.

Trial results were presented by Berenson in the poster, “Efficacy and Safety of Ruxolitinib and Steroids for Treating Patients with Relapsed or Refractory Multiple Myeloma (RRMM),” at the 62nd ASH Annual Meeting and Exposition, held virtually Dec. 5–8, 2020.

Marketed by Incyte, Jakafi is an oral inhibitor of Janus kinase 1 and 2 (JAK1/2), two enzymes involved in controlling immune and inflammatory responses, as well as in the regulation of cell proliferation. It is approved to treat bone marrow disorders like myelofibrosis or polycythemia vera, which compromise the body’s ability to create new healthy blood cells.

Preclinical studies in cellular and animal models showed that a combination of Jakafi and dexamethasone, also a corticosteroid, had anti-cancer activity against malignant myeloma cells. Among the beneficial effects reported was an ability to block the production of mucin 1, a cell surface protein that grants myeloma cells resistance to Revlimid.

This Phase 1 trial, due to conclude in September 2022, is investigating the safety and efficacy of Jakafi in combination with methylprednisolone and Revlimid in heavily pre-treated, relapsed or refractory myeloma patients in the U.S.

The first 28 patients enrolled received a combination of all three agents. Data for this trial group, recently published in the journal Clinical Cancer Research, showed that the combination therapy was well-tolerated and able to trigger promising treatment responses. Nearly half (46%) experienced some sort of clinical benefit from treatment, and about a third (28%) saw their cancer partly or fully eradicated.

Importantly, all 12 patients who responded to treatment had previously failed to respond to Revlimid, meaning they were refractory to the medication. These responses indicated the combination therapy had successfully restored an ability to respond to Revlimid.

Now, Berenson and his colleagues presented data in a second trial group. Participants were treated with a combination of Jakafi (15 mg, twice daily) and methylprednisolone (40 mg, every other day). Revlimid was added to this combination only when patients showed signs of disease progression.

As of July 25, a total of 16 patients had been enrolled in this group and 15 had completed at least one treatment cycle, making them eligible for efficacy analyses. All had undergone three to 10 prior lines of therapy, including Revlimid and steroids, and failed to respond.

More than half (53%, or 8 of the 15) saw their disease stabilize or improve to some degree, and around a third (33%, 5 patients) responded at least partly to treatment. Treatment responses lasted between one month and one year.

Six patients showed signs of disease worsening while on Jakafi and methylprednisolone, and three of them started responding to Revlimid once this medication was added.

The double combination therapy was again found to be safe and well-tolerated, without any unexpected side effects. Four patients had serious side effects and two died during the study, one from pneumonia and the other from disease progression.

“These results demonstrate that RUX [ruxolitinib] with only steroids is also well tolerated and shows promising efficacy for treating heavily previously treated MM patients,” the investigators wrote.

Based on these findings, Onco — which specializes in managing clinical trials — is planning to expand this study to further investigate the potential of Jakafi and methylprednisolone in heavily pre-treated multiple myeloma patients, including those with poor kidney function.