Early results from the Clinical Trials Alliance in Oncology randomized clinical trials of adults with relapsing multiple myeloma in frontline treatment of lenalidomide show that adding ixazomib (Ninlaro®) to pomalidomide and dexamethasone as part of second-line treatment prolonged the time patients lived before being treated. . Exacerbation of disease (progression-free survival) compared to patients who received pomalidomide and dexamethasone.
The Data and Safety Monitoring Board (DSMB) that oversees the trial recommended the National Cancer Institute (NCI) release the results because a recent interim analysis showed a significant improvement in progression-free survival for patients who received xazomib plus pomalidomide and dexamethasome.
As recommended by the DSMB, patients currently receiving pomalidomide, dexamethasone, and ixazomib should continue treatment as planned. Any patient currently receiving pomalidomide and dexamethasone may choose to receive ixazomib after discussion with the physician or to continue on 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 the Phase I/II trial known as Alliance A061202, patients in Phase I received increasing doses of pomalidomide, dexamethasone and ixazomib over a period of 28 days to determine the most tolerable dose as part of the combination, and were treated until their disease progressed or patients had unacceptable toxicity. Patients enrolled in the phase II study were required to have either proteasome inhibitor naïve or sensitive disease that had developed on lenalidomide as part of front-line treatment of multiple myeloma (eg, disease progression on frontline lenalidomide maintenance therapy). Patients were randomized to one of the two treatment arms.
We found that pomalidomide, xazomib, and dexamethasone can be safely combined. The initial efficacy of this combination is promising and requires additional investigation in phase III trials. Our results provide support for the use of this whole oral regimen for patients with lenalidomide-resistant multiple myeloma who require second-line therapy, an increasing number of patients that has not been well evaluated in randomized studies to date.. “
Peter Voorhees, MD, lead study investigator and chair, multiple myeloma specialist and chief of the division of plasma cell disorders, Levine Cancer Institute
Alliance A061202 was designed and sponsored by Alliance, and conducted by the NCI National Clinical Trial Network (NCTN) for researchers led by the Clinical Trials Alliance in Oncology. Pomalidomide was introduced by Celgene Corporation (now part of Bristol-Myers Squibb). Millennium Pharmaceuticals Inc.: Takeda Oncology provided ixazomib. Ixazomib, an oral proteasome inhibitor, may stop the growth of cancer cells by blocking certain enzymes needed for cell growth. It is currently approved by the US 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 treatment.
“We have found this whole-oral approach to be well-tolerated and distinctly active in refractory lenalidomide patients, with the benefit of an appropriate outpatient regimen, which has been shown to be feasible and particularly common among our patients during the pandemic,” commented the lead researcher and committee. Medicine, director of the Clinical Program and Clinical Research Guide, Jerome Lieber Center for Multiple Myeloma, Dana-Farber Cancer Institute in Boston, Massachusetts, whose site was the study’s principal registrar.
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 developing multiple myeloma is 1 in 132, according to the American Cancer Society, which has estimated that this year, more than 34,900 new cases will be diagnosed and about 12,410 deaths are expected.
Survival of patients with multiple myeloma has improved significantly with the advent of the immunomodulating 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 have frequent relapses and eventually succumb to refractory disease.
Alliance for Clinical Trials in Oncology