Proteasome inhibitor meets primary end point of improvement in PFS in relapsed or refractory multiple myeloma

February 11, 2015

A pivotal phase 3 trial evaluating the safety and efficacy of investigational ixazomib (Takeda), the first oral proteasome inhibitor (PI), conducted in patients with relapsed or refractory multiple myeloma achieved its primary end point of improving progression-free survival (PFS) at the first pre-specified interim analysis.

A pivotal phase 3 trial evaluating the safety and efficacy of investigational ixazomib (Takeda), the first oral proteasome inhibitor (PI), conducted in patients with relapsed or refractory multiple myeloma achieved its primary end point of improving progression-free survival (PFS) at the first pre-specified interim analysis.

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In the international, randomized, double-blind, placebo-controlled TOURMALINE-MM1 trial, patients treated with ixazomib plus lenalidomide and dexamethasone lived without their disease worsening for a significantly longer time compared to patients who received placebo plus lenalidomide/dexamethasone.

The study (n=722) was designed to compare the efficacy and safety of 2 treatment regimens administered until progression-ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone-in adult patients with relapsed and/or refractory multiple myeloma.

Participants included in the study had a confirmed diagnosis of multiple myeloma, received 1 to 3 prior therapies and meet other outlined eligibility criteria. Patients who were refractory to lenalidomide or proteasome inhibitor-based therapy were excluded.

Patients were randomly assigned to receive ixazomib 4.0 mg days 1, 8 and 15 or placebo with lenalidomide 25 mg days 1 through 21 and dexamethasone 40 mg days 1, 8, 15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria.

Dr Esseltine

“Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma; however, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients,” said Dixie-Lee Esseltine, MD, FRCPC, vice president, Oncology Clinical Research, Takeda. “The ability to demonstrate that an oral, once-weekly PI can extend PFS is a potentially important finding in the effort to address these challenges.”