Multiple myeloma patients who failed prior Revlimid (lenalidomide) treatment may benefit from a triple oral combo treatment with Ninlaro (ixazomib), Pomalyst (pomalidomide) and dexamethasone, the results of a Phase 1/2 clinical study suggest.
The research, “Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma,” appeared in the journal Leukemia.
Despite recent improvements in myeloma treatment with the introduction of new medications, often in double or triple combo therapies, a significant number of patients still relapse. These patients, particularly those refractory to Velcade (bortezomib) or the immunomodulatory treatment Revlimid, show discouraging outcomes.
Proteasome inhibitors, which block the cellular complex responsible for the breakdown of proteins — called proteasome — have become a standard treatment for myeloma patients since the introduction of Velcade. Although some of their initial limitations have been addressed, inconvenient treatment regimens and the risk of cardiovascular toxicity remain ongoing problems.
Ninlaro is a proteasome inhibitor that showed antitumor activity and good tolerability either as a single treatment or in combination with other medications.
In a prior Phase 3 trial (NCT01564537), adding Ninlaro to a regimen with Revlimid and the corticosteroid dexamethasone improved patients’ progression-free survival, the length of time without the disease worsening after starting a new treatment. These results led to the approval of this triple combo for the treatment of relapsed multiple myeloma.
To further explore the safe combination of Ninlaro with immunomodulatory medications and to find an alternative for patients refractory to Revlimid, researchers tested Pomalyst, which had shown the ability to kill tumors and effectively stimulate the immune system in this patient subgroup.
Researchers studied the safety, tolerability, and effectiveness of a weekly oral combo with Ninlaro, Pomalyst, and dexamethasone in adult patients with relapsed or refractory multiple myeloma, including those who had failed to respond to Revlimid.
In the multicenter, Phase 1/2 trial (NCT02119468), 32 patients received 3 or 4 mg of Ninlaro, 4 mg of Pomalyst, and 40 mg of dexamethasone, except those aged 75 or older, who took 20 mg of dexamethasone.
In the Phase 1 stage to determine appropriate dosing, 3 mg and 4 mg of Ninlaro were tested in two subgroups of three patients each.
Results revealed that one patient in each Ninlaro dose group developed neutropenia, or low levels of neutrophils in the blood, and thrombocytopenia, or low levels of platelets in the blood. The lower dose also led to severe fatigue and lung infection in one patient.
This prompted the use of 4 mg of Ninlaro in the Phase 2 stage, which included 25 patients over a median follow-up of 11.9 months.
Based on International Myeloma Working Group (IMWG) criteria, the treatment resulted in at least a partial response, which means a reduction in tumor size, in 12 patients (48%), with five patients exhibiting very good partial remission. The therapy also led to stable disease status in 76% of patients.
The most frequent adverse events in Phase 2 were anemia, neutropenia, thrombocytopenia, and infections.
The study supports the clinical utility of the oral triplet regimen of Ninlaro, Pomalyst, and dexamethasone for relapsed or relapsed/refractory multiple myeloma patients who are refractory to Revlimid, the researchers stated.
“The tolerability of this regimen allows its use for extended durations as evidenced by several patients who are still on study for over 2 years,” they added.
The results warrant further studies with control groups to identify the clinical benefit with the triple combo, researchers noted.