Clinical trial shows preliminary efficacy of all-oral regimen for patients with lenalidomide-refractory multiple myeloma

Early results from an Alliance for Clinical Trials in Oncology randomized clinical trial of adults with multiple myeloma relapsing on frontline lenalidomide therapy showed that adding ixazomib (Ninlaro®) to pomalidomide and dexamethasone as part of second line therapy extended the length of time patients lived before their disease worsened (progression-free survival) compared with patients who received pomalidomide and dexamethasone.

The Data and Safety Monitoring Board (DSMB) overseeing the trial recommended to the National Cancer Institute (NCI) that the results be released because a recent interim analysis showed a significant improvement in progression-free survival for those patients who received ixazomib in addition to pomalidomide and dexamethasome.

According to the DSMB's recommendation, patients currently receiving pomalidomide, dexamethasone, and ixazomib should continue therapy as planned. Any patient who is currently receiving pomalidomide and dexamethasone may elect to receive ixazomib after discussion with their physician or continue with their current regimen and add ixazomib at the time of disease progression. Full details from this study will be presented at an upcoming scientific meeting and in a peer-reviewed publication.

In a phase I/II trial known as Alliance A061202, patients in phase I received increasing doses of pomalidomide, dexamethasone, and ixazomib over a 28-day cycle to establish a maximally tolerated dose for each as part of the combination, and were treated until their disease progressed or the patients experience unacceptable toxicities. Patients enrolled in the phase II study were required to have proteasome inhibitor naïve or sensitive disease that had progressed on lenalidomide as part of frontline treatment for multiple myeloma (e.g., progression of disease on frontline lenalidomide maintenance therapy). Patients were randomized to one of the two treatment arms.

We found that pomalidomide, ixazomib, and dexamethasone can be combined safely. The preliminary efficacy of this combination is promising and warrants additional investigation in phase III trials. Our results provide support for the use of this all-oral regimen for patients with lenalidomide-refractory multiple myeloma in need of second line therapy, a growing patient population that has not been evaluated well in randomized studies to date."

Peter Voorhees, MD, Study Lead Investigator and Chair, Multiple Myeloma Specialist and Chief of the Plasma Cell Disorders Division, Levine Cancer Institute

Alliance A061202 was designed and sponsored by Alliance, and conducted by the NCI National Clinical Trials Network (NCTN) of researchers led by the Alliance for Clinical Trials in Oncology. Celgene Corporation (now part of Bristol-Myers Squibb) provided the pomalidomide. Millennium Pharmaceuticals: A Takeda Oncology Company provided the ixazomib. Ixazomib, an oral proteasome inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is currently approved by the U.S. Food and Drug Administration (FDA) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

"We found this all oral combination approach generally well tolerated and clearly active in lenalidomide-refractory patients, with the benefit of a convenient out-patient regimen, which proved especially practical and popular amongst our patients during the pandemic," commented senior investigator and Committee Chair Paul Richardson, MD, Clinical Program Leader and Directory of Clinical Research, the Jerome Lipper Multiple Myeloma Center, Dana- Farber Cancer Institute in Boston, Massachusetts, whose site was the lead enroller to the study.

Multiple myeloma is a cancer of the plasma cells that develops in the bone marrow and can spread throughout the body. It is a rare cancer. In the United States, the lifetime risk of getting multiple myeloma is 1 in 132, according to the American Cancer Society, which estimated that this year, more than 34,900 new cases will be diagnosed and about 12,410 deaths expected to occur.

Survival of patients with multiple myeloma has significantly improved with the advent of the immunomodulatory drugs, thalidomide and lenalidomide, pomalidomide, and the proteasome inhibitors bortezomib, carfilzomib and Ixazomib, as well as the introduction of monoclonal antibody therapy, including daratumumab. However, most patients will experience repeated relapses and eventually succumb to refractory disease.