Updated data with oral proteasome inhibitor reported in newly diagnosed multiple myeloma patients

An investigational all-oral proteasome inhibitor-MLN9708 (Millennium: The Takeda Oncology Company)-plus lenalidomide and dexamethasone generated high response rates and increased depth of response with extended treatment duration in newly diagnosed multiple myeloma patients, according to data presented at the American Society of Hematology (ASH) 2013 annual meeting in New Orleans.

Specifically, results showed a combined complete response and very good partial response rate of 76% (46/62) and a 94% overall response rate (ORR; 58/62 ≥ partial response). Stringent complete response was reached in 75% of patients who attained complete response.

In this phase 1/2 study, patients (phase 1: n=14; phase 2: n=57) received MLN9708, lenalidomide and dexamethasone for up to 16, 21-day cycles, followed by MLN9708 maintenance until progression or unacceptable toxicity. Transplant-eligible patients could undergo stem cell collection after ≥4 cycles and discontinue for autologous stem cell transplant (ASCT) after ≥8 cycles.

“This study is part of the ongoing evaluation of oral investigational MLN9708, and looked at combination therapy of MLN9708 with lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients,” said presenter Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston.

· For the phase 1 trial, the objective was to determine the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose.

· The recommended phase 2 dose primary objective is to determine response rates (CR+VGPR) and further evaluate safety and tolerability.

“MLN9708 is the first all oral proteasome inhibitor, IMiD [immunomodulatory drug] combination under investigation in this setting to date,” Dr Richardson said. “The safety profile, high response rates, and increased depth of response with extended treatment duration in newly diagnosed multiple myeloma patients supports MLN9708’s feasibility and activity. Based on data from this and another phase 1/2 study, we are further exploring MLN9708 in the TOURMALINE [a series of phase 3 clinical trails evaluating MLN9708] development program using a once-a-week dosing schedule.”