Evaluating ixazomib, cyclophosphamide and dexamethasone treatment for relapsed/refractory multiple myeloma

This article investigated the safety and effectiveness of combining ixazomib (Ninlaro), cyclophosphamide (Cytoxan) and dexamethasone (Decadron) for the treatment of relapsed or refractory (does not respond to treatment) multiple myeloma (RRMM). The authors concluded that the combination treatment is safe and gave the greatest benefit to patients over 65 years old.

Multiple myeloma (MM) is a cancer of plasma cells. These are a type of white blood cell normally responsible for producing antibodies. Bortezomib-based therapy is the standard treatment for these patients. However, it is associated with damage to the nerves of the hands and feet causing weakness, numbness, and pain. It also requires once to twice weekly clinic visits for administration. 

An alternative treatment is with a proteasome inhibitor ixazomib (blocks enzymes that break down proteins). This treatment in combination with cyclophosphamide (a chemotherapy drug that stops or slows cancer cell growth) and dexamethasone (anti-inflammatory steroid drug) has been shown to induce rapid and long-standing responses in relapsed patients. However, the effect on overall survival and safety of ixazomib, cyclophosphamide, and dexamethasone combination is still under investigation.

This study involved 78 patients with RRMM. They received an average of 12 cycles of ixazomib, cyclophosphamide, and dexamethasone. They were followed up for an average of 15.2 months.

Overall, 48% of patients responded to treatment. The response rate was 64% in patients aged 65 and older and 32% in patients younger than 65 years. Patients aged 65 and older were 38% less likely to have disease progression compared with patients younger than 65 years. 

For all patients, progression-free survival (PFS; the time it took for cancer to start growing again) was 14.2 months. Patients 65 and older tended to have a longer PFS (18.7 months) compared to those younger than 65 (12 months).

The most common side effects reported included diarrhea (33%), nausea (24%), respiratory infections (24%) and low platelet count (cells involved in blood clotting; 22%). Damage to the nerves of the hands and feet was reported in 10 patients.

The study concluded that the combination of ixazomib, cyclophosphamide, and dexamethasone is safe and effective in patients with RRMM.

This study had a rather small number of patients and short follow-up. Further studies are needed.

This study was funded by Millennium Pharmaceuticals, Inc., the manufacturer of ixazomib.