Ixazomib Maintenance Therapy in Chinese Patients with Newly Diagnosed Multiple Myeloma Not Treated with Stem Cell Transplantation: A Single-Arm, Open-Label Study

Introduction: Multiple myeloma (MM) is a life-threatening cancer of plasma cells in the bone marrow. It often leads to bone marrow failure and bone destruction. Lenalidomide is the only drug approved by Food and Drug Administration (FDA) and European Medical Association (EMA) as maintenance therapy for MM post stem cell transplantation (SCT), however it is not approved as maintenance for patients who are ineligible for high-dose therapy followed by SCT and is also not suitable for all patients due to toxicity and new primary malignancy (NPM) concerns. Hence, new maintenance agents are needed to offer patients continuous disease control while maintaining their health-related quality of life (HRQoL). Ixazomib, an oral protease inhibitor, was approved by FDA for MM patients with at least one prior therapy. The present study assessed the long-term safety, tolerability and efficacy of ixazomib maintenance therapy in Chinese newly diagnosed MM (NDMM) patients who had not undergone SCT. Methods: The C16021 CCS (NCT03748953) was a single arm, open-label extension of the TOURMALINE-MM4 (NCT02312258) phase 3 clinical trial, and was conducted from June 2018 to October 2022. It included Chinese patients aged ≥18 years with a confirmed diagnosis of symptomatic NDMM who had achieved a major response [complete response (CR), very good partial response (VGPR), or partial response (PR)] with initial MM therapy. Patients received oral ixazomib capsules at days 1, 8, and 15 of every 28-day cycle. The dose of ixazomib was escalated from 3 mg to 4 mg if it was tolerated during the first 4 cycles. The duration of treatment was approximately 24 months or until patients experienced progressive disease (PD) or unacceptable toxicity, whichever occurred first. The primary objective was to assess long-term safety and tolerability of ixazomib. The secondary endpoints included progression free survival (PFS), overall survival (OS), time to progression (TTP), time to next line therapy (TTNT), incidence of new primary malignancy (NPM) and HRQoL. Results: A total of 37 patients were included in the study from 7 study centers in China. Of these 37 patients, 35 patients were included in the safety analysis. The dose was escalated to 4 mg at day 1 of cycle 5 in 77% of patients. A total of 34 patients (97%) experienced at least 1 treatment emergent adverse events (TEAE) with 30 patients (86%) experiencing a treatment-related TEAE and 16 patients (46%) experienced a Grade ≥3 TEAE. The most common Grade ≥3 TEAEs reported were thrombocytopenia (2 patients, 6%) and pneumonia (2 patients, 6%). No NPMs were reported. SAEs were reported in 7 patients (20%) and 2 patients (6%) had their study drug discontinued permanently due to a TEAE. Three patients (9%) experienced TEAEs of peripheral neuropathy (PN, all grade 1 or 2) and all 3 patients had resolution and improvement of PN events during the treatment period. The median time to resolution of PN events was 24.0 days and median time to improvement of PN events was 8.0 days. Overall, 33 patients were included in the efficacy analysis. The median age was 68.3 years, male 64% and female 36%, ISS stage at initial diagnosis was 21%, 30% and 48% for stage I, II and III, respectively. The median time from initiation of induction therapy to first dose of study drug was 8.9 months. With a median follow-up of 15.9 months, median PFS and TTNT were 21.3 months and 24.7 months, respectively. If counting from induction therapy, median PFS was 30.0 months. All patients were still alive at date of last contact. Three patients (9%) demonstrated deepening of response during treatment. Of note, since only 9 patients (27%) had VGPR or PR at study entry, the potential for assessing deepening of response in this study was limited to these 9 patients. Ixazomib maintenance treatment showed no negative impact on HRQoL, as measured by the EORTC QLQ-C30, EORTC QLQ-MY20, EQ-5D-5L, and EQ VAS. Conclusion: Ixazomib maintenance therapy showed a tolerable safety profile with prolonged PFS in Chinese patients and the response was maintained thus providing a valuable treatment option in NDMM patients who have not undergone SCT. The results of this study were consistent with TOURMALINE-MM4 global study.