Twice‐weekly Ninlaro (ixazomib) plus Revlimid (lenalidomide) and dexamethasone can improve long-term outcomes in patients with newly diagnosed multiple myeloma, although it’s likely more toxic than once-weekly Ninlaro, according to the results from a Phase 1/2 trial.
The findings were published in the study, “Twice‐weekly ixazomib in combination with lenalidomide‐dexamethasone in patients with newly diagnosed multiple myeloma,” in the British Journal of Haematology.
Ninlaro (ixazomib), a proteasome inhibitor developed by Takeda, is approved in the U.S. and Europe in combination with Revlimid and dexamethasone for multiple myeloma patients who have received at least one prior treatment.
The same regimen — weekly Ninlaro plus Revlimid-dexamethasone — followed by maintenance therapy with Ninlaro alone, is being investigated for patients with newly diagnosed myeloma who did not receive any systemic therapy. So far, results from two Phase 1/2 trials look promising.
Long-term data from a Phase 1/2 study (NCT01217957) revealed that 92% of patients achieved some degree of tumor reduction, with 58% reaching at least a “very good partial response.” Data from this study also supported the feasibility of long-term maintenance treatment with single-agent Ninlaro.
A parallel Phase 1/2 study (NCT01383928) has investigated the same combination regimen, but using twice-weekly Ninlaro followed by a maintenance therapy with Ninlaro alone.
Researchers now presented long-term data from this trial, including the tolerability, safety, and effectiveness of the twice-weekly treatment, over a median follow-up period of nearly four years (46.9 months).
A total of 67 patients with newly diagnosed multiple myeloma and no previous systemic therapy were enrolled.
In the Phase 1 part of the study, 14 patients received escalating doses of Ninlaro to determine the treatment’s maximum tolerated dose and a recommended dose for future clinical trials.
Patients were treated twice a week with Ninlaro, plus Revlimid and dexamethasone (with distinct schedules) for up to 16, three-week cycles in the absence of disease worsening or unacceptable toxicity, followed by maintenance with twice‐weekly Ninlaro.
The combination therapy led to high response rates, leading to a reduction in tumor burden in nearly all patients (94%). Most of them, 68%, achieved at least a “very good partial response” with a significant number, 24%, cleared of any signs of cancer.
Patients also lived without signs of disease worsening — called progression-free survival — for approximately two years (24.9 months).
Reduction of tumor size got significantly better the longer patients were on the therapy.
“Responses were rapid, deep and durable, deepening over the course of treatment,” researchers wrote. The median duration of response was 36.9 months.
In general, the regimen was well-tolerated, and long-term therapy was feasible, with 28% of patients maintaining on therapy beyond 16 cycles and proceeding to maintenance.
The therapy also did not seem to affect the ability to collect stem cells for transplant in patients following the regimen.
However, twice-weekly Ninlaro appeared to expose patients to higher toxic effects compared to the once-a-week schedule.
Although adverse events seemed similar to those reported for treatment with once-weekly Ninlaro, more patients on the twice-weekly regimen underwent dose reductions (of any agent) or discontinuation — 66% vs. 20% on once-weekly Ninlaro.
Most patients (64%) experienced severe drug‐related adverse events, the most common being rash (13%), damage to peripheral nerves (8%), and high blood sugar (8%).
No life-threatening or disabling events due to treatment were reported.
The findings demonstrate that twice‐weekly Ninlaro combined with Revlimid and dexamethasone offers promising outcomes in newly diagnosed multiple myeloma patients, “but appears to be associated with a somewhat higher toxicity burden,” researchers wrote.
“Further investigation of twice-weekly dosing is potentially warranted to define a subset of patients who are able to tolerate, and benefit from, more intensive therapy,” they added.