Effects of ixazomib maintenance in patients with newly diagnosed multiple myeloma who are not undergoing autologous stem cell transplantation

The study evaluated outcomes of ixazomib (Ninlaro) as a maintenance therapy in patients with newly diagnosed multiple myeloma (MM) not undergoing autologous stem cell transplantation (ASCT). The main finding was that ixazomib maintenance safely improved progression-free survival (PFS) in such patients.  

Maintenance therapy prolongs the effects of an initial or induction treatment. It has been shown to improve PFS in patients with newly diagnosed MM not undergoing stem cell transplantation (SCT). PFS means how long patients survive without cancer progression. No specific agent is currently approved as maintenance in patients with newly diagnosed MM who are unfit for ASCT. They generally receive immune system modulating drugs, which often cause toxicities, as both induction and maintenance. New tolerable agents are needed for such patients.

Ixazomib is a proteasome inhibitor. Proteasomes are large molecules present in all body cells. They breakdown and remove damaged proteins. MM cells rely on proteasomes to multiply and spread. Ixazomib blocks the action of proteasomes, therefore preventing myeloma cells from growing and multiplying. The safety and effectiveness of ixazomib maintenance in patients with MM that cannot undergo ASCT remain under investigation.

The study included 706 patients with newly diagnosed MM not undergoing ASCT. They underwent 6-12 months of induction (initial) therapy. 62% of the patients achieved a complete response (CR) or very good partial response (VGPR) after induction therapy. 425 patients received ixazomib and 281 received a placebo as maintenance for 24 months.

The ixazomib group had a 34.1% reduction in the risk of progression or death compared to placebo. The average PFS was 17.4 months for ixazomib and 9.4 months for placebo. Patients aged 75 years or older had 26.2% higher chances of benefitting from therapy compared to younger ones. Patients who achieved CR or VGPR after induction had 41.4% higher chances of longer PFS compared to patients with a partial response.

36.6% of patients on ixazomib versus 23.2% on placebo had severe treatment-related side effects. These included nausea, vomiting, and diarrhea. New cancers occurred similarly in both groups (5.2% with ixazomib and 6.2% with placebo). 

The authors concluded that ixazomib maintenance improved PFS without any unexpected toxicities in patients with newly diagnosed MM not undergoing ASCT.

This was a Phase-III clinical trial sponsored by Millennium Pharmaceuticals, the manufacturer of ixazomib. Ixazomib is still not approved by FDA as a maintenance therapy.