Potential Use of Ninlaro as Maintenance Therapy in Multiple Myeloma Shown in Phase 1/2 Trials

Patients with newly diagnosed multiple myeloma benefit significantly from a combination of Ninlaro (ixazomib) plus Revlimid (lenalidomide) and dexamethasone, followed by Ninlaro maintenance therapy, according to long-term follow-up data of two Phase 1/2 trials presented at the 2017 European Hematology Association annual meeting, held June 22-25 in Madrid, Spain.

Takeda‘s Ninlaro, in combination with Revlimid (lenalidomide) and dexamethasone, was approved by the U.S. Food and Drug Administration (FDA) in November 2015 and by the European Commission a year later for the treatment of multiple myeloma patients who have undergone at least one prior therapy.

Now, the two trials assessed the combination, followed by Ninlaro maintenance therapy, in newly diagnosed patients who did not undergo stem cell transplant. The results from these clinical trials were presented in two oral sessions.

The first, “Deep and Durable Responses with Weekly Ixazomib, Lenalidomide and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Long-Term Follow-up of Patients who did not Undergo SCT,” presented findings from an ongoing Phase 1/2 trial (NCT01217957) where newly-diagnosed myeloma patients received weekly oral Ninlaro in combination with Revlimid and dexamethasone for up to 12 28-day induction cycles. After the initial therapy, 25 patients continued to receive weekly Ninlaro as a single-agent therapy.

After a median follow-up of 55.2 months — more than 4.5 years — key findings from the combination part of the study included an overall response rate of 80%, with 32% complete responses.

Also, six out of seven patients who were tested for minimal residual disease (MRD) were found to be MRD-negative, which indicates a decreased chance of relapse. The median progression-free survival (PFS) was 29.4 months.

In terms of adverse events, 86% of patients suffered grade 3 or higher adverse events and 52% had serious adverse reactions.

For patients who went on to receive single-agent maintenance Ninlaro therapy, there was an increased depth of response, with 32% of patients showing improved response during maintenance therapy. There was less toxicity reported in the maintenance period compared to the induction period.

“Based on an increasing body of evidence that long-term therapy may improve clinical outcomes, this Phase 1/2 trial focused on continuous treatment of patients with newly diagnosed multiple myeloma,” lead investigator Shaji Kumar, MD, from the Mayo Clinic, said in a press release.

“The trial evaluated patients who received weekly [Ninlaro] plus lenalidomide and dexamethasone as an induction regimen followed by maintenance with single-agent [Ninlaro],” Kumar said. “Data showed that patients had deep responses on single-agent therapy and median progression-free survival of more than two years. We remain committed to gathering additional data of [Ninlaro] in this investigational, maintenance setting.”

Results from the second clinical trial (NCT01383928) were also presented in an oral session, titled “Twice Weekly Ixazomib Plus Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Data for Patients who did not Undergo Stem Cell Transplant (SCT).”

This Phase 1/2 clinical trial evaluated the administration of Ninlaro twice a week in combination with Revlimid and dexamethasone for 16 21-day cycles followed by single-agent therapy with Ninlaro.

After a median follow-up of 47 months, patients undergoing the combination therapy had an overall response rate of 92%, with a complete plus very good partial response of 69% and complete response rate of 31%. Eight out of nine patients tested for MRD were found to be MRD-negative. The median progression-free survival was 24.9 months.

Eighty-five percent of patients suffered grade 3 or higher adverse events, and 54% had serious adverse reactions. For patients who went on to receive single-agent maintenance Ninlaro therapy, 22% improved their response during treatment.

“The addition of [Ninlaro] — a first-in-class oral proteasome inhibitor — to doublet therapy has been shown to substantially improve efficacy in newly diagnosed multiple myeloma patients,” said lead investigator Paul Richardson, MD, at the Dana-Farber Cancer Institute.

“In this Phase 1/2 trial in newly diagnosed multiple myeloma, [Ninlaro] plus lenalidomide and dexamethasone resulted not only in high quality of responses using a twice a week schedule but also in an encouraging deepening of responses over time in patients who did not receive a stem cell transplant,” he said.

“In addition, impressive durable clinical benefit was seen as patients went on to receive maintenance therapy with single-agent [Ninlaro] after successful induction/remission therapy using this all-oral approach.”