Ixazomib Based Regimens As Front-Line Treatment in Newly Diagnosed Multiple Myeloma Patients in China: A Real-World Data from Infinite Study
Authors: Cheng Cheng Fu , Jin Song , Zhuang Junling , Zhou Xin , Zhou Fan , Li Yuhua , Ding Kaiyang , Niu Ting , Chen Wenming , Fang Baijun , Chen Li-Li , Fu Rong , Zhang Hao , Fu Jiaping , Wang Xiuju , Liu Sha , Li Lin , Wu Depei 
Published: December 2024

Background: Multiple myeloma (MM) poses a significant clinical challenge, characterized by its incurable nature and the need for effective therapeutic interventions. Proteasome inhibitors (PIs) are the backbone of the MM treatment, but there is not much evidence supporting intravenous PIs as continuous treatment due to adverse events (AE) such as peripheral neuropathy (PN). Ixazomib (IXA), an oral PI, has shown to improve the prognosis of patients with newly diagnosed MM (NDMM) in several clinical studies. This study mainly explores the efficacy and safety of IXA in the treatment of patients with NDMM in China.

Methods: This prospective, non-interventional study [INFINITE (NCT04328662), 2nd interim analysis] was conducted exclusively across 28 centers within China from 2020. NDMM participants who received at least one dose of an IXA-based regimen within three months from their initial treatment were recruited. All the participants were evaluated for efficacy (ORR [overall response rate], DOT [duration of treatment], PFS [progression-free survival] , OS [overall survival]) and safety (treatment-emergent AEs[TEAEs] [IXA-related TEAEs]). Time-to-event outcomes were analyzed by Kaplan-Meier method, and statistical analyses were carried out using SAS Enterprise Guide 8.3 software.

Results: At data cut-off (30 Jun 2023), 74 patients were enrolled with a median age of 67 years (range: 30-91), with 35% patients≥70 years of age, and 59.5% were males. A total of 43.8% patients were considered high-risk by Stratification of Mayo smart; 82.5% with Durie-Salmon stage III; 50.0% with ISS III; 32.1% with R-ISS III; 36.8% patients with creatinine clearance rate&lt;60ml/min. Only 2.7% patients received stem cell transplantation till last follow-up. Common concomitant diseases included hypertension 41.9%；other cardiac disorders 31.1%，including arrhythmia 2.7%, cardiac failure1.4%, angina pectoris1.4%, cardiac valve disease1.4%, myocardial ischaemia1.4%, and pericardial effusion 2.7%; infectious disease 37.8%, including pneumonia 17.6%, viral infection 6.8%, hepatitis B 4.1%; renal disorders 28.4%, including renal failure 9.5%, renal cyst 8.1%, renal impairment 5.4%, chronic kidney disease 4.1%；pulmonary disorders 18.9%, including emphysema 4.1%, pleural effusion 4.1%, pulmonary mass 4.1% , cystic lung disease 2.7% and pulmonary arterial hypertension 1.4%, and diabetes mellitus 17.6%. Of the 74 patients, 29 patients were treated with the I-based triplet regimens or Id regimen (Ixazomib-dexamethasone), while 45 patients switched from other regimens to the I-base regimen, with 30 patients (67%) transferring from the V-base regimens, primarily due to intolerance of toxicities.

After a median follow-up of 15.2 months, the median DOT was 14.5 months (95% CI: 9.4, 19.4), median PFS from initial IXA was 15.8 months (95% CI: 10.7, NR), OS was not reached. For patients with R-ISS III and those classified as high risk disease by mSMART, the median DOT were 13.8 months (4.6, 21.6) and 13.8months (5.4, 19.4). ORR in general cohort was 80%, with ≥VGPR rate 59%. In R-ISS III patients and those classified as high risk by mSMART, the ORR was 82% and 92% respectively, with ≥VGPR rates of 67% and 58% respectively. Overall, TEAEs related to IXA were 44.6%. The most common hematologic TEAE was thrombocytopenia (all grades 8.1%, ≥G3 4.1%) and anemia (all grades 5.4%, ≥G3 0%), and the most common non-hematologic TEAEs were diarrhea (all grades 17.6%, ≥G3 1.4%) and vomiting (all grades 9.5%, ≥G3 0.0%). Additionally, the incidence rates of PN and infections were 1.4% (≥3 grades 0.0%) and 5.4% (≥3 grades 0.0%), with a 1.4% occurrence rate of heart failure. Serious TEAEs and TEAEs leading to treatment discontinuation were 2.7% and 14.9%, respectively. Special interest TEAEs were observed in 9(12.2%) patients, including Cardiac failure 2.7%, Arrhythmia 1.4%, Hepatic failure 4.1%, Hepatic function abnormal 2.7%, Hypertension 1.4%).

Conclusion: In the real-world practice in China, IXA-based regimens as front-line treatment or switching from other PI regimens demonstrate good tolerability in NDMM patients, more likely in elderly with multiple comorbidities. The DOT and efficacy are similar for high-risk patients and the overall population. Our study suggests that IXA could be administrated for continuous treatment in NDMM patients.