Ixazomib plus lenalidomide and dexamethasone administered twice weekly leads to good response and long-term outcomes for patients with newly diagnosed multiple myeloma (NDMM), but the regimen may increase toxicity compared with once-weekly dosing, according to a study published in the British Journal of Haematology.

For this phase 1/2 clinical study, researchers enrolled 128 patients with NDMM and treated them with ixazomib 3.0-3.7 mg plus lenalidomide 25 mg and dexamethasone 20 mg twice weekly. Sixty-four patients each were assigned to phase 1 and 2 studies, in which investigators evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety, and efficacy. No dose-limiting toxicities were observed during phase 1, and the R2PD was set as ixazomib 3.0 mg.

Among 62 evaluable patients in the phase 2 portion of the study, the confirmed overall response rate (ORR) was 94%, which consisted of 68% of patients achieving at least very good partial response, and 24% achieving complete response. The median progression-free survival was 24.9 months. Treatment response also deepened over a median duration of 36.9 months.

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Sixty-four percent of patients in the study experienced grade 3 treatment-related adverse events (AEs), including rash, peripheral neuropathy, and hyperglycemia. No grade 4 AEs were reported.  Overall, 13 patients discontinued treatment due to AEs.

The authors concluded that “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.”


Richardson PG, Hofmeister CC, Rosenbaum CA, et al. Twice‐weekly ixazomib in combination with lenalidomide‐dexamethasone in patients with newly diagnosed multiple myeloma [published online June 25, 2018]. Br J Haematol. doi: 10.1111/bjh.15394