Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

Abstract

Background Maintenance therapy following autologous stem cell transplantation can delay disease progression and prolong survival in multiple myeloma (MM). Ixazomib is ideally suited for maintenance therapy given its efficacy, convenient once-weekly oral dosing, and low toxicity profile. Methods The phase 3, double-blind, placebo-controlled, TOURMALINE-MM3 study randomised 656 patients with newly diagnosed MM from 227 clinical/hospital sites in 30 countries in Europe, the Middle East, Africa,

Quality of life is maintained with ixazomib maintenance in post‐transplant newly diagnosed multiple myeloma: The TOURMALINE‐MM3 trial

“…The characteristics were similar to those of the overall intent-to-treat population in TOURMALINE-MM3. 13 At study entry, scores on the EORTC QLQ-C30 and EORTC QLQ-MY20 were high for functional scales and low for symptom scales and were similar between ixazomib and placebo arms.…”

“…The design and primary results of the phase 3, double-blind, placebocontrolled TOURMALINE-MM3 trial (NCT02181413) have been reported previously. 13 Briefly, eligible participants were adults with at least a partial response after induction therapy followed by high-dose melphalan conditioning and a single ASCT within 12 months of diagnosis. The induction regimen must have included a proteasome inhibitor or an immunomodulatory drug.…”

“…No difference was observed between the treatment groups in the global health domain (Global Health Status/QoL) of the EORTC QLQ -C30, which was reported as a secondary objective in the main study. 13 The aim of this analysis was to assess, in detail, the impact of ixazomib therapy compared with placebo on HRQoL, patient-reported MM-specific symptoms and functioning in TOURMALINE-MM3 in the context of an established minimal important difference (MID), or the smallest change in a patient-reported outcome (PRO) measure considered important to patients. [14][15][16] Of particular interest were the domains and items considered most clinically relevant and likely to be impacted by MM and/or MT: Global Health Status/QoL, Physical Functioning, Role Functioning, Pain, Nausea/Vomiting and Diarrhoea subscales from the EORTC QLQ -C30 plus Disease Symptoms subscale and Peripheral Neuropathy item from the EORTC QLQ-MY20.…”

“…Single-agent oral ixazomib as a MT resulted in a statistically significant improvement in PFS relative to placebo. 13 In addition, TOURMALINE-MM3 was the first trial of maintenance therapies currently used in clinical practice to assess the impact of MT on HRQoL after ASCT in patients with newly diagnosed MM. Subjects' HRQoL was evaluated using two patient-reported European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: the general EORTC Quality of Life Questionnaire Core Module 30 Disease Symptoms subscale and Peripheral Neuropathy item.…”

Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy

“…The model assumed that maintenance therapy would extend the period during which patients would remain EP or UEP, based on evidence from clinical trials demonstrating improvements concerning remission and HRQoL post-ASCT. [10][11][12][20][21][22] Although other therapies such as ixazomib have been studied as maintenance therapy in this population, 28 data from lenalidomide studies were used for estimating the impact of maintenance therapy on productivity as lenalidomide is the currently approved standard maintenance therapy in this setting. 2 per patient, which are lower than the productivity losses found in our study.…”